Rapid turnover of long noncoding RNAs and the evolution of gene expression.
Rapid turnover of long noncoding RNAs and the evolution of gene expression.
复制标题
DOI：
10.1371/journal.pgen.1002841
复制
发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Marques AC
中科院分区：
文献类型：
--
作者：
Kutter C;Watt S;Stefflova K;Wilson MD;Goncalves A;Ponting CP;Odom DT;Marques AC
哺乳动物基因组中的大部分功能序列福尔斯位于蛋白质编码外显子之外，并且可以转录成长RNA。然而，长链非编码RNA（lncRNA）在哺乳动物生物学中的作用还没有得到很好的理解。很少有lncRNA具有实验确定的作用，其中一些是谱系特异性的。如果我们要了解lncRNA基因座对哺乳动物生物学和谱系特异性性状的贡献，那么确定lncRNA基因座转录在多个进化谱系中保留或丢失的程度是至关重要的。在这里，我们通过实验研究了在密切相关的啮齿动物物种中lncRNA表达的保守性，允许DNA序列的进化与转录表达的进化解耦。我们生成了总RNA（RNAseq）和H3 K4 me 3结合（ChIPseq）的DNA数据，并将两者结合起来，构建了在小家鼠（C57 BL/6 J），小家鼠（Mus musculus castaneus）和褐家鼠（Rattus norvegicus）成年肝脏中表达的转录本目录。我们估计了lncRNA的转录周转率，并研究了它们的谱系特异性出生或死亡的影响。与蛋白质编码基因相比，LncRNA转录在啮齿动物进化过程中表现出更大的增益和损失。核苷酸取代率被发现反映了啮齿动物之间基因间lncRNA的体内转录保守性：只有具有保守转录的非编码基因座的序列受到限制。最后，我们发现谱系特异性基因间lncRNA似乎与基因组相邻蛋白质编码基因的表达适度升高有关。我们的研究结果表明，近一半的基因间lncRNA位点已经获得或丢失，因为最后的共同祖先的小鼠和大鼠，他们预测，这种快速的转录周转有助于组织和谱系特异性基因表达的进化。哺乳动物基因组中最为人所知的部分包含转录成RNA的基因，RNA随后被翻译成蛋白质。这些基因通常处于高选择压力下，并且在物种之间高度保守。最近的出版物揭示了新的基因类别，这些基因也转录成RNA，但随后不翻译成蛋白质。其中一类新的RNA是长链非编码RNA（lncRNA）。LncRNA基因座以与蛋白质编码基因类似的方式控制，但更经常地表达组织特异性，并且它们的保守性和功能大多是未知的。以前的报告表明，lncRNA可以影响附近蛋白质编码基因的表达，或者在远处控制更广泛的生物过程。此外，与蛋白质编码基因相比，lncRNA序列在哺乳动物之间的保守性较差，但它们的转录进化速度如何，特别是在密切相关的物种之间，仍然未知。通过比较两种小鼠和大鼠同源组织中lncRNA的表达，我们发现lncRNA基因比蛋白质编码基因更快地“出生”或“死亡”，并且这种快速进化会影响附近编码基因的表达水平。这种基因表达的局部调节揭示了lncRNA快速进化的功能作用，这可能有助于物种之间的生物学差异。
A large proportion of functional sequence within mammalian genomes falls outside protein-coding exons and can be transcribed into long RNAs. However, the roles in mammalian biology of long noncoding RNA (lncRNA) are not well understood. Few lncRNAs have experimentally determined roles, with some of these being lineage-specific. Determining the extent by which transcription of lncRNA loci is retained or lost across multiple evolutionary lineages is essential if we are to understand their contribution to mammalian biology and to lineage-specific traits. Here, we experimentally investigated the conservation of lncRNA expression among closely related rodent species, allowing the evolution of DNA sequence to be uncoupled from evolution of transcript expression. We generated total RNA (RNAseq) and H3K4me3-bound (ChIPseq) DNA data, and combined both to construct catalogues of transcripts expressed in the adult liver of Mus musculus domesticus (C57BL/6J), Mus musculus castaneus, and Rattus norvegicus. We estimated the rate of transcriptional turnover of lncRNAs and investigated the effects of their lineage-specific birth or death. LncRNA transcription showed considerably greater gain and loss during rodent evolution, compared with protein-coding genes. Nucleotide substitution rates were found to mirror the in vivo transcriptional conservation of intergenic lncRNAs between rodents: only the sequences of noncoding loci with conserved transcription were constrained. Finally, we found that lineage-specific intergenic lncRNAs appear to be associated with modestly elevated expression of genomically neighbouring protein-coding genes. Our findings show that nearly half of intergenic lncRNA loci have been gained or lost since the last common ancestor of mouse and rat, and they predict that such rapid transcriptional turnover contributes to the evolution of tissue- and lineage-specific gene expression. The best-understood portion of mammalian genomes contains genes transcribed into RNAs, which are subsequently translated into proteins. These genes are generally under high selective pressure and deeply conserved between species. Recent publications have revealed novel classes of genes, which are also transcribed into RNA but are not subsequently translated into proteins. One such novel class are long noncoding RNA (lncRNA). LncRNA loci are controlled in a similar manner to protein-coding genes, yet are more often expressed tissue-specifically, and their conservation and function(s) are mostly unknown. Previous reports suggest that lncRNAs can affect the expression of nearby protein-coding genes or act at a distance to control broader biological processes. Also, lncRNA sequence is poorly conserved between mammals compared with protein-coding genes, but how rapidly their transcription evolves, particularly between closely related species, remains unknown. By comparing lncRNA expression between homologous tissues in two species of mouse and in rat, we discovered that lncRNA genes are “born” or “die” more rapidly than protein-coding genes and that this rapid evolution impacts the expression levels of nearby coding genes. This local regulation of gene expression reveals a functional role for the rapid evolution of lncRNAs, which may contribute to biological differences between species.
登录
查看更多内容
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
9.8
作者：
Church DM;Goodstadt L;Hillier LW;Zody MC;Goldstein S;She X;Bult CJ;Agarwala R;Cherry JL;DiCuccio M;Hlavina W;Kapustin Y;Meric P;Maglott D;Birtle Z;Marques AC;Graves T;Zhou S;Teague B;Potamousis K;Churas C;Place M;Herschleb J;Runnheim R;Forrest D;Amos-Landgraf J;Schwartz DC;Cheng Z;Lindblad-Toh K;Eichler EE;Ponting CP;Mouse Genome Sequencing Consortium
通讯作者：
Mouse Genome Sequencing Consortium
影响因子：
3.7
作者：
de Jonge HJ;Fehrmann RS;de Bont ES;Hofstra RM;Gerbens F;Kamps WA;de Vries EG;van der Zee AG;te Meerman GJ;ter Elst A
通讯作者：
ter Elst A
影响因子：
48
作者：
Cloonan, Nicole;Forrest, Alistair R. R.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.