The evolution of spliceosomal introns

Current Opinion in Genetics and Development

Volumn 12, Issue 6, 2002, Pages 701-710

  Lynch, Michael ^a   Richardson, Aaron O ^a  

^a INDIANA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GENOMIC RNA; MESSENGER RNA; PROTEIN;

CELL PROLIFERATION; EUKARYOTE EVOLUTION; GENE FUNCTION; GENE MUTATION; GENE SEQUENCE; GENE STRUCTURE; GENETIC ANALYSIS; GENETIC CODE; GENETIC DRIFT; GENETIC SELECTION; HYPOTHESIS; INTRON; MOLECULAR GENETICS; NONHUMAN; PHYLOGENY; PRIORITY JOURNAL; REVIEW; SPLICEOSOME; ANIMAL; GENETICS; GENOME; HUMAN; MOLECULAR EVOLUTION;

EUKARYOTA;

ANIMALS; EVOLUTION, MOLECULAR; GENOME; HUMANS; INTRONS; SPLICEOSOMES;

EID: 0036888952     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(02)00360-X     Document Type: Review

References (115)

1. Doolittle W.F. Genes in pieces: were they ever together? Nature. 272:1978;581-582.
2. Cavalier-Smith T. Selfish DNA and the origin of introns. Nature. 315:1985;283-284.
3. Gilbert W. The exon theory of genes. Cold Spring Harb Symp Quant Biol. 52:1987;901-905.
4. Rogers J.H. How were introns inserted into nuclear genes? Trends Genet. 5:1989;213-216.
5. Palmer J.D., Logsdon J.M. Jr. The recent origins of introns. Curr Opin Genet Dev. 1:1991;470-477.
6. Logsdon J.M. Jr. The recent origins of spliceosomal introns revisited. Curr Opin Genet Dev. 8:1998;637-648.
7. Stiller J.W., Duffield E.C., Hall B.D. Amitochondriate amoebae and the evolution of DNA-dependent RNA polymerase II. Proc Natl Acad Sci USA. 95:1998;11769-11774.
8. Fast N.M., Doolittle W.F. Trichomonas vaginalis possesses a gene encoding the essential spliceosomal component, PRP8. Mol Biochem Parasitol. 99:1999;275-278.
9. Archibald J.M., O'Kelly C.J., Doolittle W.F. The chaperonin genes of jakobid and jakobid-like flagellates: implications for eukaryotic evolution. Mol Biol Evol. 19:2002;422-431. A demonstration that members of two early branching protist lineages, the jakobids and malawimonads, harbor large numbers of spliceosomal introns, supporting the ancientness of the spliceosome within eukaryotes.
10. Nixon J.E., Wang A., Morrison H.G., McArthur A.G., Sogin M.L., Loftus B.J., Samuelson J. A spliceosomal intron in Giardia lamblia. Proc Natl Acad Sci USA. 99:2002;3701-3705. Drawing from the results of a genomic sequencing project involving the putatively basal eukaryotic lineage, this study provides evidence for the very early existence of the eukaryotic spliceosome.
11. Lynch M. Intron evolution as a population-genetic process. Proc Natl Acad Sci USA. 99:2002;6118-6123. A focus on the excess deleterious mutation rate of intron-containing alleles, introducing the population-genetic theory for the ability of introns to proliferate in populations of different effective sizes.
12. Long M., Rosenberg C., Gilbert W. Intron phase correlations and the evolution of the intron/exon structure of genes. Proc Natl Acad Sci USA. 92:1995;12495-12499.
13. de Souza S.J., Long M., Klein R.J., Roy S., Lin S., Gilbert W. Toward a resolution of the introns early/late debate: only phase zero introns are correlated with the structure of ancient proteins. Proc Natl Acad Sci USA. 95:1998;5094-5099.
14. Roy S.W., Lewis B.P., Fedorov A., Gilbert W. Footprints of primordial introns on the eukaryotic genome. Trends Genet. 17:2001;496-501.
15. Sharp P.A. On the origin of RNA splicing and introns. Cell. 42:1985;397-400.
16. Cech T.R. The generality of self-splicing RNA: relationship to nuclear mRNA splicing. Cell. 44:1986;207-210.
17. Jacquier A. Self-splicing group II and nuclear pre-mRNA introns: how similar are they? Trends Biochem Sci. 15:1990;351-354.
18. Cavalier-Smith T. Intron phylogeny: a new hypothesis. Trends Genet. 7:1991;145-148.
19. Dai L., Zimmerly S. Compilation and analysis of group II intron insertions in bacterial genomes: evidence for retroelement behavior. Nucleic Acids Res. 30:2002;1091-1102. A large-scale bioinformatic survey demonstrating that eubacterial group II introns are generally absent from conserved genes, often fragmented, and very frequently located in intergenic regions. This suggests that such elements are subject to high rates of gain and loss and behave largely as retroelements rather than as introns.
20. Bonen L., Vogel J. The ins and outs of group II introns. Trends Genet. 17:2001;322-331. A review of group II intron splicing and mobility that offers tantalizing parallels to the theory of reverse splicing in spliceosomal introns.
21. Burge C.B., Tuschl T., Sharp P.A. Splicing of precursors to mRNAs by the spliceosomes. Gesteland R.F., Cech T.R., Atkins J.F., The RNA World. 2nd edn:1999;525-560 Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
22. Michel F., Ferat J.-L. Structure and activities of group II introns. Annu Rev Biochem. 64:1995;435-461.
23. Valadkhan B., Manley J.L. Intrinsic metal binding by a spliceosomal RNA. Nat Struct Biol. 9:2002;498-499. The authors review recent findings on striking biochemical similarities between splicing involving group II introns and the spliceosome.
24. Sontheimer E.J., Gordon P.M., Piccirilli J.A. Metal ion catalysis during group II intron self-splicing: parallels with the spliceosome. Genes Dev. 13:1999;1729-1741.
25. Yean S.L., Wuenschell G., Termini J., Lin R.J. Metal-ion coordination by U6 small nuclear RNA contributes to catalysis in the spliceosome. Nature. 408:2000;881-884. By manipulating the metal-ion environment of the yeast spliceosome, Yean et al. provide biochemical support for the idea that RNA forms the catalytic heart of the spliceosome.
26. Shukla G.C., Padgett R.A. A catalytically active group II intron domain 5 can function in the U12-dependent spliceosome. Mol Cell. 9:2002;1145-1150. The authors demonstrate that a domain of a group II intron can functionally substitute for the U6 snRNA of the spliceosome, strengthening the case that the spliceosome arose out of a fragmented ancestral group II element.
27. Hetzer M., Wurzer G., Schweyen R.J., Mueller M.W. Trans-activation of group II intron splicing by nuclear U5 snRNA. Nature. 386:1997;417-420.
28. Weiner A.M. mRNA splicing and autocatalytic introns: distant cousins or the products of chemical determinism. Cell. 72:1993;161-164.
29. Malek O., Knoop V. Trans-splicing group II introns in plant mitochondria: the complete set of cis-arranged homologs in ferns, fern allies, and a hornwort. RNA. 4:1998;1599-1609.
30. Lambowitz A.M., Caprara M.G., Zimmerly S., Perlman P.S. Group I and group II ribozymes as RNPs: clues to the past and guides to the future. Gesteland R.F., Cech T.R., Atkins J.F., The RNA World. 2nd edn:1999;451-486 Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
31. Cousineau B., Lawrence S., Smith D., Belfort M. Retrotransposition of a bacterial group II intron. Nature. 404:2000;1018-1021. Thefirst demonstration of an invasion of a group II intron into an ectopic position: a result of clear relevance to the group II origin hypothesis for spliceosomal introns.
32. Hiller R., Hetzer M., Schweyen R.J., Mueller M.W. Transposition and exon shuffling by group II intron RNA molecules in pieces. J Mol Biol. 297:2000;301-308. Hiller et al. provide empirical evidence that fragmented group II introns from yeast mitochondria can function in trans to support intron transposition. This is one of several recent studies that support the contention that RNA-based movements of introns can facilitate the production of new introns and shuffled exons.
33. Zimmerly S., Hausner G., Wu X. Phylogenetic relationships among group II intron ORFs. Nucleic Acids Res. 29:2001;1238-1250. A phylogenetic analysis of eubacterial group II intron reverse transcriptase that suggests a bacterial origin of organelle group II introns. A significant amount of horizontal transfer of such introns among prokaryotes is also suggested, raising difficulties for identifying their ultimate source.
34. Vogel J., Borner T., Hess W.R. Comparative analysis of splicing of the complete set of chloroplast group II introns in three higher plant mutants. Nucleic Acids Res. 27:1999;3866-3874.
35. Jenkins B.D., Barkan A. Recruitment of a peptidyl-tRNA hydrolase as a facilitator of group II intron splicing in chloroplasts. EMBO J. 20:2001;872-879. The authors identify and characterize one of the nuclear-encoded proteins that are necessary for the splicing of chloroplast group II introns. A gene possibly arising from duplication of a peptidyl-tRNA hydrolase has apparently been recruited for use in the splicing of group II introns.
36. Stoltzfus A. On the possibility of constructive neutral evolution. J Mol Evol. 49:1999;169-181.
37. Force A., Lynch M., Pickett B., Amores A., Yan Y.L., Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics. 151:1999;1531-1545.
38. Lynch M., O'Hely M., Walsh B., Force A. The probability of fixation of a newly arisen gene duplicate. Genetics. 159:2001;1789-1804. We develop a population-genetic theory for the fixation probabilities of subfunctionalized (or fragmented) genes following gene duplication.
39. Hall S.L., Padgett R.A. Conserved sequences in a class of rare eukaryotic nuclear introns with non-consensus splice sites. J Mol Biol. 239:1994;357-365.
40. Burge C.B., Padgett R.A., Sharp P.A. Evolutionary fates and origins of U12-type introns. Mol Cell. 2:1998;773-785.
41. Will C.L., Schneider C., Reed R., Luhrmann R. Identification of both shared and distinct proteins in the major and minor spliceosomes. Science. 284:1999;2003-2005.
42. Will C.L., Schneider C., MacMillan A.M., Katopodis N.F., Neubauer G., Wilm M., Luhrmann R., Query C.C. A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site. EMBO J. 20:2001;4536-4546. One of several recent demonstrations that the proteins involved in splicing are generally shared between the major and minor spliceosomes.
43. Schneider C., Will C.L., Makarova O.V., Makarov E.M., Luhrmann R. Human U4/U6.U5 and U4atac/U6atac. U5 tri-snRNPs exhibit similar protein compositions. Mol Cell Biol. 22:2002;3219-3229. An immunoprecipitation study that demonstrates remarkable similarity in the overall protein composition of the major and minor spliceosomes.
44. Luo H.R., Moreau G.A., Levin N., Moore M.J. The human Prp8 protein is a component of both U2- and U12-dependent spliceosomes. RNA. 5:1999;893-908.
45. Toor N., Hausner G., Zimmerly S. Coevolution of group II intron RNA structures with their intron-encoded reverse transcriptases. RNA. 7:2001;1142-1152. A bioinformatic survey that suggests that the RNA structures of group II introns coevolve with intron-encoded reverse transcriptases.
46. Levine A., Durbin R. A computational scan for U12-dependent introns in the human genome sequence. Nucleic Acids Res. 29:2001;4006-4013. From a scan of the genome sequence, the authors develop a reference list of putative U12-dependent introns in humans, and from a parallel analysis of cDNAs, they present data suggesting that these introns tend to be inaccurately spliced out.
47. Patel A.A., McCarthy M., Steitz J.A. The splicing of U12-type introns can be a rate-limiting step in gene expression. EMBO J. 21:2002;3804-3815. Present studies with constructs involving human and Drosophila cell lines that demonstrate that U12-dependent introns are spliced out of pre-mRNAs more slowly than are U2-dependent introns. These results may help explain the relative rarity of U12-dependent introns.
48. Logsdon J.M. Jr, Stoltzfus A., Doolittle W.F. Molecular evolution: recent cases of spliceosomal intron gain? Curr Biol. 8:1998;R560-R563.
49. O'Neill R.J.W., Brennan F.E., Delbridge M.L., Crozier R.H., Graves J.A.M. De novo insertion of an intron into the mammalian sex determining gene, SRY. Proc Natl Acad Sci USA. 95:1998;1653-1657.
50. Robertson H.M. The large srh family of chemoreceptor genes in Caenorhabditis nematodes reveals processes of genome evolution involving large duplications and deletions and intron gains and losses. Genome Res. 10:2000;192-203. A thorough investigation of a large group of chemoreceptor genes in C. elegans that provides a qualitative glimpse of intron turnover. Duplicate genes may provide a powerful opportunity for quantifying the rates of such events, as homology of intron positions among paralogous genes can often be confidently assigned.
51. Krzywinski J., Besansky N.J. Frequent intron loss in the White gene: a cautionary tale for phylogeneticists. Mol Biol Evol. 19:2002;362-366. The mapping of intron presence in the White gene of dipterans on a phylogenetic tree, showing frequent loss of introns (and possibly gain at the same loci) across species.
52. Kent W.J., Zahler A.M. Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment. Genome Res. 10:2000;1115-1125. An early bioinformatic comparison of homologous regions of the C. elegans and C. briggsae genomes, which we use to estimate the rates of intron turnover in this genus. With the recently sequenced genome of C. briggsae now being annotated, a more sophisticated analysis should be possible in the near future.
53. Coghlan A., Wolfe K.H. Fourfold faster rate of genome rearrangement in nematodes than in Drosophila. Genome Res. 12:2002;857-867. A large-scale comparison of the C. elegans and C. briggsae genomes, with an attempt to date the common ancestor of these two species.
54. Moriyama E.N., Petrov D.A., Hartl D.L. Genome size and intron size in Drosophila. Mol Biol Evol. 15:1998;770-773.
55. Russo C.A., Takezaki N., Nei M. Molecular phylogeny and divergence times of drosophilid species. Mol Biol Evol. 12:1995;391-404.
56. Fink G.R. Pseudogenes in yeast? Cell. 49:1986;5-6.
57. Wada H., Kobayashi M., Sato R., Satoh N., Miyasaka H., Shirayama Y. Dynamic insertion-deletion of introns in deuterostome EF-1( genes. J Mol Evol. 54:2002;118-128. The authors provide evidence for both gain and loss of spliceosomal introns during deuterostome evolution, showing that introns tend to be lost individually instead of all at once (the expectation if whole processed mRNA is reverse transcribed and recombined with genomic DNA).
58. Llopart A., Comeron J.M., Brunet F.G., Lachaise D., Long M. Intron presence-absence polymorphism in Drosophila driven by positive Darwinian selection. Proc Natl Acad Sci USA. 99:2002;8121-8126. Llopart et al. report the discovery of a polymorphism for intron presence in Drosophila and examine neighboring sequence for evidence of recent selection. They suggest that the mode of intron loss involved simple genomic deletion rather than reverse transcription of cDNA.
59. Rogers J.H. The role of introns in evolution. FEBS Lett. 268:1990;339-343.
60. Venkatesh B., Ning Y., Brenner S. Late changes in spliceosomal introns define clades in vertebrate evolution. Proc Natl Acad Sci USA. 96:1999;10267-10271.
61. Purugganan M., Wessler S. The splicing of transposable elements and its role in intron evolution. Genetica. 86:1992;295-303.
62. Giroux M.J., Clancy M., Baier J., Ingham L., McCarty D., Hannah L.C. De novo synthesis of an intron by the maize transposable element Dissociation. Proc Natl Acad Sci USA. 91:1994;12150-12154.
63. Kidwell M.G., Lishch D.R. Perspective: Transposable elements, parasitic DNA, and genome evolution. Evolution. 55:2001;1-24.
64. Bhattacharya D., Lutzoni F., Reeb V., Simon D., Nason J., Fernandez F. Widespread occurrence of spliceosomal introns in the rDNA genes of ascomycetes. Mol Biol Evol. 17:2000;1971-1984.
65. Clement J., Maiti S., Wilkinson M.F. Localization and stability of introns spliced from the Pem homeobox gene. J Biol Chem. 20:2001;16919-16930. This paper is relevant to the mechanisms of intron spread in that it provides estimates of the rate of intron degradation after splicing and also presents evidence of a spliced intron in the cytoplasm.
66. Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., et al. Initial sequencing and analysis of the human genome. Nature. 409:2001;860-921. A first broad look at the emerging human genome sequence.
67. Esnault C., Maestre J., Heidmann T. Human LINE retrotransposons generate processed pseudogenes. Nat Genet. 24:2000;363-367. Esnault et al. demonstrate that LINE-encoded reverse transcriptase can be diverted to mRNAs unassociated with LINEs, thereby providing a powerful mechanism for the production of processed pseudogenes.
68. Weiner A. SINEs and LINEs: the art of biting the hand that feeds you. Curr Opin Cell Biol. 14:2002;343-350. A synthetic review of the basic biology of short and long interspersed retrotransposable elements.
69. Iborra F.J., Jackson D.A., Cook P.R. Coupled transcription and translation within nuclei of mammalian cells. Science. 293:2001;1139-1142. An exciting empirical demonstration that at least a small amount of translation occurs within the nuclear membrane. This observation is a major deviation from the current dogma that translation is restricted to the cytoplasm, and if correct, has implications for how introns can be gained and lost through the modification of mRNAs.
70. Stoltzfus A., Logsdon J.M. Jr, Palmer J.D., Doolittle W.F. Intron 'sliding' and the diversity of intron positions. Proc Natl Acad Sci USA. 94:1997;10739-10744.
71. Tarrio R., Rodriguez-Trelles F., Ayala F.J. New Drosophila introns originate by duplication. Proc Natl Acad Sci USA. 95:1998;1658-1662.
72. Hankeln T., Friedl H., Ebersberger I., Martin J., Schmidt E.R. A variable intron distribution in globin genes of Chironomus: evidence for recent intron gain. Gene. 205:1997;151-160.
73. Maniatis T., Reed R. An extensive network of coupling among gene expression machines. Nature. 416:2002;499-506. A grand synthetic overview of the mechanisms by which mRNAs are processed en route to their final destination at the ribosomes, demonstrating that the chain of processing events are linked through various shared proteins.
74. Ares M. Jr, Grate L., Pauling M.H. A handful of intron-containing genes produces the lion's share of yeast mRNA. RNA. 5:1999;1138-1139.
75. Fong Y.W., Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 414:2001;929-933. One of a growing list of studies showing that splicing is intimately related to other mRNA processing events and demonstrating that the spliceosomal small ribonucleoproteins function to promote the recruitment of the transcriptional-elongation apparatus.
76. Luo M.J., Reed R. Splicing is required for rapid and efficient mRNA export in metazoans. Proc Natl Acad Sci USA. 96:1999;14937-14942.
77. Reed R., Hurt E. A conserved mRNA export machinery coupled to pre-mRNA splicing. Cell. 108:2002;523-531. Another in a series of studies demonstrating the interconnections between splicing and other mRNA processing events, this one reviewing evidence for a tight coupling between mRNA export and pre-mRNA splicing.
78. Dye M.J., Proudfoot N.J. Terminal exon definition occurs cotranscriptionally and promotes termination of RNA polymerase II. Mol Cell. 3:1999;371-378.
79. McCracken S., Lambermon M., Blencowe B.J. SRm160 splicing coactivator promotes transcript 3′-end cleavage. Mol Cell Biol. 22:2002;148-160. Identification of an SR protein that acts as a coactivator of splicing and also participates in 3′ end formation of transcripts.
80. Niwa M., MacDonald C.C., Berget S.M. Are vertebrate exons scanned during splice-site selection? Nature. 360:1992;277-280.
81. Niwa M., Rose S.D., Berget S.M. In vitro polyadenylation is stimulated by the presence of an upstream intron. Genes Dev. 4:1990;1552-1559.
82. Long M., Deutsch M. Association of intron phases with conservation at splice site sequences and evolution of spliceosomal introns. Mol Biol Evol. 16:1999;1528-1534.
83. Liu H.X., Zhang M., Krainer A.R. Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins. Genes Dev. 12:1998;1998-2012.
84. Schaal T.D., Maniatis T. Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. Mol Cell Biol. 19:1999;1705-1719.
85. Blencowe B.J. Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem Sci. 25:2000;106-110. A review on the role that ESEs play in guiding the splicing apparatus and on the deleterious consequences of the modification of such sites.
86. Graveley B.R. Sorting out the complexity of SR protein functions. RNA. 6:2000;1197-1211. A timely review of the accessory roles that SR proteins play in splicing.
87. Cooper T.A., Mattox W. The regulation of splice-site selection, and its role in human disease. Am J Hum Genet. 61:1997;259-266.
88. Nissim-Rafinia M., Kerem B. Splicing regulation as a potential genetic modifier. Trends Genet. 18:2002;123-127. A review of how changes in splicing motifs can influence splicing patterns, thereby affecting phenotypic variation and disease expression.
89. Fedorov A., Saxonov S., Fedorova L., Daizadeh I. Comparison of intron-containing and intron-lacking human genes elucidates putative exonic splicing enhancers. Nucleic Acids Res. 29:2001;1464-1469. A novel bioinformatic investigation that identifies oligomers that are enriched in intron-containing genes relative to intron-free genes. Such an approach may provide a powerful route to characterizing general exon splicing enhancers and silencers.
90. Fairbrother W.G., Yeh R.F., Sharp P.A., Burge C.B. Predictive identification of exonic splicing enhancers in human genes. Science. 297:2002;1007-1013. A large bioinformatic evaluation of putative ESEs in the human genome, combined with an empirical verification of their function in vivo.
91. Duret L., Mouchiroud D. Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci USA. 96:1999;4482-4487.
92. Aravind L., Watanabe H., Lipman D.J., Koonin E.V. Lineage-specific loss and divergence of functionally linked genes in eukaryotes. Proc Natl Acad Sci USA. 97:2000;11319-11324. A broad comparison of the compete genomic sequences of the two yeasts S. cerevisiae and S. pombe demonstrating, among other things, that the former species has lost many of the spliceosomal components that are conserved in other eukaryotic lineages.
93. Käufer N.F., Potashkin J. Analysis of the splicing machinery in fission yeast: a comparison with budding yeast and mammals. Nucleic Acids Res. 28:2000;3003-3010. A bioinformatic survey demonstrating that sequences of splicing factors in S. cerevisiae have diverged more from those of human than have those of S. pombe, in accordance with the hypothesis that the S. cerevisiae splicing machinery is unusual.
94. Zhao X.F., Nowak N.J., Shows T.B., Aplan P.D. MAGOH interacts with a novel RNA-binding protein. Genomics. 63:2000;145-148. Zhao et al. identify a key protein involved in the exon junction complex of both arthropods and mammals, and note that it appears to be absent from S. cerevisiae.
95. Abovich N., Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 89:1997;403-412.
96. Wood V., Gwilliam R., Rajandream M.A., Lyne M., Lyne R., Stewart A., Sgouros J., Peat N., Hayles J., Baker S., et al. The genome sequence of Schizosaccharomyces pombe. Nature. 415:2002;871-880. This paper contains a wealth of information, comparing the genome of S. pombe to that of S. cerevisiae and revealing that the former has approximately twenty times more introns than the latter.
97. Hentze M.W., Kulozik A.E. A perfect message: RNA surveillance and nonsense-mediated decay. Cell. 96:1999;307-310.
98. Gonzalez C.I., Bhattacharya A., Wang W., Peltz S.W. Nonsense-mediated mRNA decay in Saccharomyces cerevisiae. Gene. 274:2001;15-25. Gonzalez et al. provide a broad review of the known properties of the NMD pathway in yeast.
99. Lykke-Andersen J. mRNA quality control: marking the message for life or death. Curr Biol. 11:2001;R88-R91. An overview of the mechanisms of NMD in mammals and yeast.
100. Mango S.E. Stop making nonSense: the C. elegans smg genes. Trends Genet. 17:2001;646-653. Mango offers some speculations on the operation of NMD in nematodes.
101. Maquat L.E., Carmichael G.G. Quality control of mRNA function. Cell. 104:2001;173-176. Another easily digested review of NMD.
102. Wilusz C.J., Wang W., Peltz S.W. Curbing the nonsense: the activation and regulation of mRNA surveillance. Genes Dev. 15:2001;2781-2785. Yet another review of the rapidly emerging findings on NMD.
103. Frischmeyer P.A., Dietz H.C. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet. 8:1999;1893-1900.
104. Nagy E., Maquat L.E. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci. 6:1998;198-199.
105. Maquat L.E., Li X. Mammalian heat shock p70 and histone H4 transcripts, which derive from naturally intronless genes, are immune to nonsense-mediated decay. RNA. 7:2001;445-456. A key paper demonstrating that naturally intronless genes in mouse and human fail to elicit NMD when they are engineered to contain a premature termination codon.
106. Brocke K.S., Neu-Yilik G., Gehring N.H., Hentze M.W., Kulozik A.E. The human intronless melanocortin 4-receptor gene is NMD insensitive. Hum Mol Genet. 11:2002;331-335. Another demonstration (see also [105••] ) that introns are generally required if a human gene containing a premature termination codon is to be silenced by NMD.
107. Ruiz-Echevarria M.J., González C.I., Peltz S.W. Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA. EMBO J. 17:1998;575-589.
108. Mendell J.T., Medghalchi S.M., Lake R.G., Noensie E.N., Dietz H.C. Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes. Mol Cell Biol. 20:2000;8944-8957. Another in a line of studies demonstrating the functional interrelationships between various steps in processing and surveillance of mRNAs.
109. Cheng J., Belgrader P., Zhou X., Maquat L.E. Introns are cis-effectors of the nonsense-codon-mediated reduction in nuclear mRNA abundance. Mol Cell Biol. 14:1994;6317-6325.
110. Zhang J., Sun X., Qian Y., LaDuca J.P., Maquat L.E. At least one intron is required for the nonsense-mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation. Mol Cell Biol. 18:1998;5272-5283.
111. Rajavel K.S., Neufeld E.F. Nonsense-mediated decay of human HEXA mRNA. Mol Cell Biol. 21:2001;5512-5519. One of the first demonstrations that NMD can sometimes occur in human genes free of introns, thereby suggesting a backup pathway that relies on sequences within coding regions for orientation with respect to the position of correct termination codons.
112. Pulak R., Anderson P. mRNA surveillance by the Caenorhabditis elegans smg genes. Genes Dev. 7:1993;1885-1897.
113. Neu-Yilik G., Gehring N.H., Thermann R., Frede U., Hentze M.W., Kulozik A.E. Splicing and 3′ end formation in the definition of nonsense-mediated decay-competent human β-globin mRNPs. EMBO J. 20:2001;532-540. One of the few studies that provides information, albeit of a qualitative nature, on the spatial constraints of the NMD process.
114. Isshiki M., Yamamoto Y., Satoh H., Shimamoto K. Nonsense-mediated decay of mutant waxy mRNA in rice. Plant Physiol. 125:2001;1388-1395. One of the few studies to address the operation of NMD in plants; there is room for considerable work in this area.
115. Castillo-Davis C.I., Mekhedov S.L., Hartl D.L., Koonin E.V., Kondrashov F.A. Selection for short introns in highly expressed genes. Nat Genet. 31:2002;415-418. CastilloDavis et al. demonstrate that highly expressed genes have smaller introns and speculate that this is a consequence of selection for rapid mRNA processing. By contrast, the number of introns appears to be independent of expression level, suggesting that additional factors must be responsible for the latter.