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Functional Implications of RNA Splicing for Human Long Intergenic Noncoding RNAs.

Chen FC, Pan CL, Lin HY - Evol. Bioinform. Online (2014)

Bottom Line: The majority of annotated human lincRNAs include multiple exons and are alternatively spliced.The evolutionary path of hominid-specific lincRNAs thus seemed to have diverged from that of their more ancestral counterparts.In addition, the SEL-MEL and ASE-CSE differences implied that splicing might be important for the functionality or regulations of lincRNAs in primates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Population Health Sciences, National Health Research Institutes, Taiwan. ; Department of Biological Science and Technology, National Chiao-Tung University, Taiwan. ; Department of Dentistry, China Medical University, Taiwan.

ABSTRACT
Long intergenic noncoding RNAs (lincRNAs) have been suggested as playing important roles in human gene regulation. The majority of annotated human lincRNAs include multiple exons and are alternatively spliced. However, the connections between alternative RNA splicing (AS) and the functions/regulations of lincRNAs have remained elusive. In this study, we compared the sequence evolution and biological features between single-exonic lincRNAs and multi-exonic lincRNAs (SELs and MELs, respectively) that were present only in the hominoids (hominoid-specific) or conserved in primates (primate-conserved). The MEL exons were further classified into alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs) for evolutionary analyses. Our results indicate that SELs and MELs differed significantly from each other. Firstly, in hominoid-specific lincRNAs, MELs (both CSEs and ASEs) evolved slightly more rapidly than SELs, which evolved approximately at the neutral rate. In primate-conserved lincRNAs, SELs and ASEs evolved slightly more slowly than CSEs and neutral sequences. The evolutionary path of hominid-specific lincRNAs thus seemed to have diverged from that of their more ancestral counterparts. Secondly, both of the exons and transcripts of SELs were significantly longer than those of MELs, and this was probably because SEL transcripts were more resistant to RNA splicing than MELs. Thirdly, SELs were physically closer to coding genes than MELs. Fourthly, SELs were more widely expressed in human tissues than MELs. These results suggested that SELs and MELs represented two biologically distinct groups of genes. In addition, the SEL-MEL and ASE-CSE differences implied that splicing might be important for the functionality or regulations of lincRNAs in primates.

No MeSH data available.


Related in: MedlinePlus

The genetic distances in lincRNA exons between (A) human and orangutan; and (B) human and rhesus macaque.Notes: Statistical significance: *P < 0.05; ***P < 0.001 by Wilcoxon Rank Sum test.
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f1-ebo-10-2014-219: The genetic distances in lincRNA exons between (A) human and orangutan; and (B) human and rhesus macaque.Notes: Statistical significance: *P < 0.05; ***P < 0.001 by Wilcoxon Rank Sum test.

Mentions: We first examined whether the primary sequences of SELs and MELs were subject to different levels of selective constraint. A recent report indicated that mammal-conserved lincRNAs tended to be SELs.18 We were thus interested to know whether SELs were more conserved than MELs for evolutionarily recent (H-O and H-Ma) lincRNAs. We also classified the exons of MELs into CSEs and ASEs to examine whether splicing was associated with the evolution of lincRNAs. For H-O lincRNAs, unexpectedly, CSEs and ASEs had slightly larger genetic distances than pure introns and intergenic regions. Meanwhile, the H-O genetic distances of SELs were approximately the same as those of the non-exonic regions (Fig. 1A). This observation seemed to suggest that SELs were selectively neutral, whereas the evolution of CSEs and ASEs was slightly accelerated.


Functional Implications of RNA Splicing for Human Long Intergenic Noncoding RNAs.

Chen FC, Pan CL, Lin HY - Evol. Bioinform. Online (2014)

The genetic distances in lincRNA exons between (A) human and orangutan; and (B) human and rhesus macaque.Notes: Statistical significance: *P < 0.05; ***P < 0.001 by Wilcoxon Rank Sum test.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4264600&req=5

f1-ebo-10-2014-219: The genetic distances in lincRNA exons between (A) human and orangutan; and (B) human and rhesus macaque.Notes: Statistical significance: *P < 0.05; ***P < 0.001 by Wilcoxon Rank Sum test.
Mentions: We first examined whether the primary sequences of SELs and MELs were subject to different levels of selective constraint. A recent report indicated that mammal-conserved lincRNAs tended to be SELs.18 We were thus interested to know whether SELs were more conserved than MELs for evolutionarily recent (H-O and H-Ma) lincRNAs. We also classified the exons of MELs into CSEs and ASEs to examine whether splicing was associated with the evolution of lincRNAs. For H-O lincRNAs, unexpectedly, CSEs and ASEs had slightly larger genetic distances than pure introns and intergenic regions. Meanwhile, the H-O genetic distances of SELs were approximately the same as those of the non-exonic regions (Fig. 1A). This observation seemed to suggest that SELs were selectively neutral, whereas the evolution of CSEs and ASEs was slightly accelerated.

Bottom Line: The majority of annotated human lincRNAs include multiple exons and are alternatively spliced.The evolutionary path of hominid-specific lincRNAs thus seemed to have diverged from that of their more ancestral counterparts.In addition, the SEL-MEL and ASE-CSE differences implied that splicing might be important for the functionality or regulations of lincRNAs in primates.

View Article: PubMed Central - PubMed

Affiliation: Institute of Population Health Sciences, National Health Research Institutes, Taiwan. ; Department of Biological Science and Technology, National Chiao-Tung University, Taiwan. ; Department of Dentistry, China Medical University, Taiwan.

ABSTRACT
Long intergenic noncoding RNAs (lincRNAs) have been suggested as playing important roles in human gene regulation. The majority of annotated human lincRNAs include multiple exons and are alternatively spliced. However, the connections between alternative RNA splicing (AS) and the functions/regulations of lincRNAs have remained elusive. In this study, we compared the sequence evolution and biological features between single-exonic lincRNAs and multi-exonic lincRNAs (SELs and MELs, respectively) that were present only in the hominoids (hominoid-specific) or conserved in primates (primate-conserved). The MEL exons were further classified into alternatively spliced exons (ASEs) and constitutively spliced exons (CSEs) for evolutionary analyses. Our results indicate that SELs and MELs differed significantly from each other. Firstly, in hominoid-specific lincRNAs, MELs (both CSEs and ASEs) evolved slightly more rapidly than SELs, which evolved approximately at the neutral rate. In primate-conserved lincRNAs, SELs and ASEs evolved slightly more slowly than CSEs and neutral sequences. The evolutionary path of hominid-specific lincRNAs thus seemed to have diverged from that of their more ancestral counterparts. Secondly, both of the exons and transcripts of SELs were significantly longer than those of MELs, and this was probably because SEL transcripts were more resistant to RNA splicing than MELs. Thirdly, SELs were physically closer to coding genes than MELs. Fourthly, SELs were more widely expressed in human tissues than MELs. These results suggested that SELs and MELs represented two biologically distinct groups of genes. In addition, the SEL-MEL and ASE-CSE differences implied that splicing might be important for the functionality or regulations of lincRNAs in primates.

No MeSH data available.


Related in: MedlinePlus