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灵长类动物中微小RNA的进化

Evolution of microRNA in primates.

作者信息

McCreight Jey C, Schneider Sean E, Wilburn Damien B, Swanson Willie J

机构信息

Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

出版信息

PLoS One. 2017 Jun 22;12(6):e0176596. doi: 10.1371/journal.pone.0176596. eCollection 2017.

Abstract

MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny. Hundreds of miRNA were validated, and the number of species with experimentally validated miRNA was tripled. These species include a sister taxon to humans (bonobo) and basal primates (aye-aye, mouse lemur, galago). Consistent with previous studies, we found the seed region and mature miRNA to be highly conserved across primates, with overall structural conservation of the pre-miRNA hairpin. However, there were a number of interesting exceptions, including a seed shift due to structural changes in miR-501. We also identified an increase in the number of miR-320 paralogs throughout primate evolution. Many of these non-conserved miRNA appear to regulate neuronal processes, illustrating the importance of investigating miRNA to learn more about human evolution.

摘要

微小RNA在人类基因组中大多数转录本的转录后调控中发挥着重要作用,但其在灵长类谱系中的进化情况在很大程度上尚不明确。一种特定的微小RNA可以有一个到数千个信使RNA靶标,这使得序列上的微小变化或微小RNA的整体结构变化有可能产生深远的表型效应。然而,大多数非人类灵长类微小RNA仅通过与人类基因组的同源性来预测,缺乏实验验证。在本研究中,我们对代表广泛灵长类系统发育的13个物种进行了测序。数百种微小RNA得到了验证,经过实验验证的微小RNA的物种数量增加了两倍。这些物种包括人类的姐妹分类群(倭黑猩猩)和基础灵长类动物(指猴、鼠狐猴、婴猴)。与之前的研究一致,我们发现种子区域和成熟微小RNA在灵长类动物中高度保守,前体微小RNA发夹结构整体保守。然而,也有一些有趣的例外情况,包括由于miR - 501结构变化导致的种子移位。我们还发现在整个灵长类进化过程中,miR - 320旁系同源物的数量有所增加。许多这些不保守的微小RNA似乎调控神经元过程,这说明了研究微小RNA对于深入了解人类进化的重要性。

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