Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian Genes

Shabalina, Svetlana A.; Ogurtsov, Aleksey Y.; Spiridonov, A. N.; Novichkov, Pavel S.; Spiridonov, Nikolay A.; Koonin, Eugene V.

doi:10.1093/molbev/msq086

Cited by 123 publications

(109 citation statements)

References 29 publications

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“…The low number of introns has also been noted in putative lncRNAs obtained in some but not all large-scale studies (Ravasi et al 2006;Guttman et al 2010;Ørom et al 2010). It has been shown that at least among protein-coding RNAs, the intron-less transcripts as a group have a lower transcriptional expression level and a more tissue-specific expression pattern compared with spliced messages (Shabalina et al 2010). Furthermore, the intron- less mRNAs were evolutionarily younger, showed lower interspecies sequence conservation, and seemed to code disproportionately for regulatory proteins (Shabalina et al 2010).…”

Section: Architecture Of Lncrna Transcriptsmentioning

confidence: 90%

“…To elucidate features unique to this class of functional RNAs, a parallel analysis was performed on a database containing all human protein-coding genes. The results revealed the presence of several common sequence features among lncRNAs, including the paucity or absence of introns and the low GC content, which could at least partly explain the nuclear localization and low expression levels observed in many lncRNAs (Kelly and Corbett 2009;Shabalina et al 2010). A detailed analysis of their proteincoding capacity indicated that while the lncRNAs do contain short ORFs, their poor start codon context makes efficient translation unlikely.…”

Section: Introductionmentioning

confidence: 95%

“…It has been shown that at least among protein-coding RNAs, the intron-less transcripts as a group have a lower transcriptional expression level and a more tissue-specific expression pattern compared with spliced messages (Shabalina et al 2010). Furthermore, the intron- less mRNAs were evolutionarily younger, showed lower interspecies sequence conservation, and seemed to code disproportionately for regulatory proteins (Shabalina et al 2010). While the evolutionary and functional significance of splicing in lncRNAs is yet to be determined, many of the characteristics listed above for intron-less protein-coding genes are also prominent features found in the majority of lncRNAs Mercer et al 2009;Ponting et al 2009;Wilusz et al 2009;Guttman et al 2010).…”

Section: Architecture Of Lncrna Transcriptsmentioning

confidence: 99%

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Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3′ UTRs

Niazi

Valadkhan²

2012

RNA

152

127

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Recent transcriptome analyses have indicated that a large part of mammalian genomes are transcribed into long non-proteincoding RNAs (lncRNAs). However, only a very small fraction of them have been individually studied, and whether the majority of lncRNAs found in large-scale studies have a cellular role is debated. To gain insight into the sequence features and genomic architecture of the subset of lncRNAs that have been proven to be functional, we created a database containing studied lncRNAs manually culled from the literature along with a parallel database containing all annotated protein-coding human RNAs. The Functional lncRNA Database, which contains 204 lncRNAs and their splicing variants, is available at valadkhanlab.org/database. Analysis of the lncRNAs and their comparison to protein-coding transcripts revealed sequence features including paucity of introns and low GC content in lncRNAs, which could explain several biological characteristics of these transcripts, such as their nuclear localization and low expression level. The predicted ORFs in lncRNAs have poor start codon and ORF contexts, which would lead to activation of the nonsense-mediated decay pathways and thus make it unlikely for most lncRNAs to code for even short peptides. Interestingly, our analyses revealed significant similarities between the lncRNAs and the 39 untranslated regions (39 UTRs) in protein-coding RNAs in structural features and sequence composition. The presence of these intriguing parallels between the lncRNAs and 39 UTRs, which constitute the two main components of the RNA-mediated cellular regulatory system, indicates that highly similar evolutionary constraints govern the function of regulatory RNA sequences in the cell.

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Section: Architecture Of Lncrna Transcriptsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 95%

Section: Architecture Of Lncrna Transcriptsmentioning

confidence: 99%

See 1 more Smart Citation

Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3′ UTRs

Niazi

Valadkhan²

2012

RNA

152

127

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“…It has been suggested that older duplicates undergo more alternative splicing than recent duplicates (Kopelman et al 2005;Su et al 2006;Shabalina et al 2010). We dated duplication events using tree reconciliation from Ensembl Compara (Vilella et al 2009), which allows higher resolution than previously used methods.…”

Section: Age Mattersmentioning

confidence: 99%

Age-dependent gain of alternative splice forms and biased duplication explain the relation between splicing and duplication

Roux

Robinson‐Rechavi

2010

Genome Res.

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We analyze here the relation between alternative splicing and gene duplication in light of recent genomic data, with a focus on the human genome. We show that the previously reported negative correlation between level of alternative splicing and family size no longer holds true. We clarify this pattern and show that it is sufficiently explained by two factors. First, genes progressively gain new splice variants with time. The gain is consistent with a selectively relaxed regime, until purifying selection slows it down as aging genes accumulate a large number of variants. Second, we show that duplication does not lead to a loss of splice forms, but rather that genes with low levels of alternative splicing tend to duplicate more frequently. This leads us to reconsider the role of alternative splicing in duplicate retention.

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“…A lthough the vast majority of pre-mRNAs in higher eukaryotes contain introns, 5% of human protein-coding genes do not contain introns (1). However, these naturally intronless mRNAs encode proteins of critical importance, including the histones, the c-Jun proto-oncoprotein, and the antiviral IFN proteins.…”

mentioning

confidence: 99%

Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex

Lei

Dias²,

Reed³

2011

Proc. Natl. Acad. Sci. U.S.A.

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A great deal is known about the export of spliced mRNAs, but little is known about the export of mRNAs encoded by human cellular genes that naturally lack introns. Here, we investigated the requirements for export of three naturally intronless mRNAs (HSPB3, . Significantly, we found that all three mRNAs are stable and accumulate in the cytoplasm, whereas sizematched random RNAs are unstable and detected only in the nucleus. A portion of the coding region confers this stability and cytoplasmic localization on the naturally intronless mRNAs and a cDNA transcript, which is normally retained in the nucleus and degraded. A polyadenylation signal, TREX mRNA export components, and the mRNA export receptor TAP are required for accumulation of the naturally intronless mRNAs in the cytoplasm. We conclude that naturally intronless mRNAs contain specific sequences that result in efficient packaging into the TREX mRNA export complex, thereby supplanting the splicing requirement for efficient mRNA export.A lthough the vast majority of pre-mRNAs in higher eukaryotes contain introns, 5% of human protein-coding genes do not contain introns (1). However, these naturally intronless mRNAs encode proteins of critical importance, including the histones, the c-Jun proto-oncoprotein, and the antiviral IFN proteins. In addition, many viral genes lack introns. Because most genes in higher eukaryotes contain introns, understanding the gene expression of naturally intronless genes has lagged behind that of intron-containing genes.Studies over the past several years have revealed that splicing is not only essential for removing introns but also plays important roles in numerous other steps in gene expression because of functional coupling among the different steps. For example, splicing is coupled to RNA polymerase II (RNAP II) transcription, 3′ end formation, mRNA stability, mRNA export, translation, and cytoplasmic localization of mRNA (2-5). Several studies indicate that mRNAs generated by splicing are both more stable and more efficiently exported to the cytoplasm than their cDNA transcript counterparts (6, 7). This splicing-dependent enhancement of mRNA stability/export is because of, at least in part, recruitment of the conserved transcription/export (TREX) complex, which contains the multisubunit THO complex and the proteins UAP56, Aly, Tex1, and CIP29 (6-8). In vitro studies showed that the human TREX complex associates with the 5′ end of mRNAs during splicing through an interaction between Aly and the cap-binding complex (9, 10). Because splicing occurs cotranscriptionally, the human TREX complex is indirectly recruited to mRNA during transcription (4, 9). In contrast, in yeast, in which most genes lack introns, the TREX complex is directly recruited to mRNA during transcription and 3′ end formation (11-13). The interactions between the 3′ end formation machinery and the TREX complex are conserved from yeast to humans, indicating that a role for 3′ end formation in mRNA export is also likely in humans (13).The RNA processing machin...

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Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian Genes

Cited by 123 publications

References 29 publications

Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3′ UTRs

Computational analysis of functional long noncoding RNAs reveals lack of peptide-coding capacity and parallels with 3′ UTRs

Age-dependent gain of alternative splice forms and biased duplication explain the relation between splicing and duplication

Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complex

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