小柯机器人

脊椎动物极端保守5'非翻译区的功能和结构基础
2021-04-07 14:10

美国斯坦福大学医学院Maria Barna研究组取得最新进展。他们揭示脊椎动物5'非翻译区极端保守的功能和结构基础。2021年4月5日出版的《自然-遗传学》杂志发表了该成果。

他们揭示了极端保守的5'非翻译区(UTRs)在非典型翻译调控中的意外作用,该调控与脊椎动物物种关键发育特征的出现有关。这些5'UTRs中保守元件的内源敲除降低了基因表达水平,而高度保守的5'UTRs具有顺式调节元件,可促进细胞类型特异性翻译调控。

他们进一步绘制了细胞内突变和图谱(icM2),这是一种映射细胞内RNA结构的新方法。使用icM2,他们确定了一个极其保守的5'UTR编码多个可变结构,并且该保守元件内的每个单个核苷酸都维持了对控制蛋白质表达动态范围重要的可变结构平衡。

这些结果解释了极端序列保守性如何导致脊椎动物基因组非翻译区中编码的RNA级生物学功能。

据了解,缺乏关于基因组极端保守性的知识仍然是人们对基因调控进化的认识上的一个主要空白。

附:英文原文

Title: Functional and structural basis of extreme conservation in vertebrate 5′ untranslated regions

Author: Gun Woo Byeon, Elif Sarinay Cenik, Lihua Jiang, Hua Tang, Rhiju Das, Maria Barna

Issue&Volume: 2021-04-05

Abstract: The lack of knowledge about extreme conservation in genomes remains a major gap in our understanding of the evolution of gene regulation. Here, we reveal an unexpected role of extremely conserved 5′ untranslated regions (UTRs) in noncanonical translational regulation that is linked to the emergence of essential developmental features in vertebrate species. Endogenous deletion of conserved elements within these 5′ UTRs decreased gene expression, and extremely conserved 5′ UTRs possess cis-regulatory elements that promote cell-type-specific regulation of translation. We further developed in-cell mutate-and-map (icM2), a new methodology that maps RNA structure inside cells. Using icM2, we determined that an extremely conserved 5′ UTR encodes multiple alternative structures and that each single nucleotide within the conserved element maintains the balance of alternative structures important to control the dynamic range of protein expression. These results explain how extreme sequence conservation can lead to RNA-level biological functions encoded in the untranslated regions of vertebrate genomes.

DOI: 10.1038/s41588-021-00830-1

Source: https://www.nature.com/articles/s41588-021-00830-1

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

分享到:

0