Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cell. 2011 Dec 23;147(7):1537-50. doi: 10.1016/j.cell.2011.11.055.
Thousands of long intervening noncoding RNAs (lincRNAs) have been identified in mammals. To better understand the evolution and functions of these enigmatic RNAs, we used chromatin marks, poly(A)-site mapping and RNA-Seq data to identify more than 550 distinct lincRNAs in zebrafish. Although these shared many characteristics with mammalian lincRNAs, only 29 had detectable sequence similarity with putative mammalian orthologs, typically restricted to a single short region of high conservation. Other lincRNAs had conserved genomic locations without detectable sequence conservation. Antisense reagents targeting conserved regions of two zebrafish lincRNAs caused developmental defects. Reagents targeting splice sites caused the same defects and were rescued by adding either the mature lincRNA or its human or mouse ortholog. Our study provides a roadmap for identification and analysis of lincRNAs in model organisms and shows that lincRNAs play crucial biological roles during embryonic development with functionality conserved despite limited sequence conservation.
在哺乳动物中已经鉴定出了数千种长的间隔非编码 RNA(lincRNA)。为了更好地理解这些神秘 RNA 的进化和功能,我们使用染色质标记、poly(A)-位点映射和 RNA-Seq 数据,在斑马鱼中鉴定了超过 550 种不同的 lincRNA。尽管这些 lincRNA 与哺乳动物 lincRNA 有许多共同特征,但只有 29 种具有与假定的哺乳动物直系同源物的可检测序列相似性,通常仅限于单个短的高保守区域。其他 lincRNA 具有保守的基因组位置,而没有可检测的序列保守性。针对两个斑马鱼 lincRNA 保守区域的反义试剂导致了发育缺陷。针对剪接位点的试剂也会导致相同的缺陷,并且通过添加成熟的 lincRNA 或其人类或小鼠直系同源物可以得到挽救。我们的研究为鉴定和分析模式生物中的 lincRNA 提供了路线图,并表明 lincRNA 在胚胎发育过程中发挥着至关重要的生物学作用,尽管序列保守性有限,但功能仍然保守。