Chen Feng-Chi, Pan Chia-Lin, Lin Hsuan-Yu
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.
Institute of Population Health Sciences, National Health Research Institutes, Taiwan.
Evol Bioinform Online. 2014 Dec 10;10:219-28. doi: 10.4137/EBO.S20772. eCollection 2014.
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.
长链基因间非编码RNA（lincRNA）被认为在人类基因调控中发挥重要作用。大多数已注释的人类lincRNA包含多个外显子，并且存在可变剪接。然而，可变RNA剪接（AS）与lincRNA的功能/调控之间的联系仍然不清楚。在本研究中，我们比较了仅存在于类人猿中的单外显子lincRNA和多外显子lincRNA（分别为SEL和MEL）之间的序列进化和生物学特征，这些lincRNA在类人猿中是特异性的，或者在灵长类中是保守的。MEL外显子进一步分为可变剪接外显子（ASE）和组成型剪接外显子（CSE）用于进化分析。我们的结果表明，SEL和MEL彼此之间存在显著差异。首先，在类人猿特异性lincRNA中，MEL（CSE和ASE）的进化速度略快于SEL，而SEL大约以中性速率进化。在灵长类保守的lincRNA中，SEL和ASE的进化速度略慢于CSE和中性序列。因此，人类特异性lincRNA的进化路径似乎与其更古老的对应物有所不同。其次，SEL的外显子和转录本都明显长于MEL，这可能是因为SEL转录本比MEL更抗RNA剪接。第三，SEL在物理上比MEL更接近编码基因。第四，SEL在人类组织中的表达比MEL更广泛。这些结果表明，SEL和MEL代表了两组生物学上不同的基因。此外，SEL-MEL和ASE-CSE的差异意味着剪接可能对灵长类中lincRNA的功能或调控很重要。
