Alcohol Research Center, Department of Psychiatry, University of Connecticut Health Center, Farmington, CT 06030, USA.
Nucleic Acids Res. 2011 Jan;39(2):701-11. doi: 10.1093/nar/gkq798. Epub 2010 Sep 22.
Recent deep-sequencing efforts have identified many novel non-conserved small RNAs that are expressed at low levels in certain mammalian cells. Whether these small RNAs are important for mammalian physiology is debatable, therefore we explored the function of one such RNA, human miR-1271. This small RNA is similar in sequence to miR-96, a highly conserved microRNA that when mutated causes hearing loss in humans and mice. Although the miR-1271 and miR-96 sequences differ slightly, our in vitro assays indicate that they have an identical regulatory activity. We have identified brain-expressed mRNAs from genes including, GPHN, RGS2, HOMER1 and KCC2, which share the same miR-96 and miR-1271 regulatory elements. Interestingly, human miR-1271 is expressed abundantly in brain tissue, where miR-96 is not highly expressed. The rodent miR-1271 precursor contains several sequence differences in the precursor stem, which appear to reduce the efficiency of microRNA processing. Our data indicate that although miR-1271 and miR-96 function identically in vitro, they function to some extent uniquely in vivo. Given the expression patterns and nature of the target genes, miR-1271 may have a significant, although non-conserved, role in regulating aspects of neural development or function in humans.
最近的深度测序研究已经鉴定出许多新型的非保守性小 RNA，它们在某些哺乳动物细胞中低水平表达。这些小 RNA 是否对哺乳动物生理学很重要还存在争议，因此我们研究了一种这样的 RNA，人类 miR-1271。这种小 RNA 的序列与 miR-96 相似，miR-96 是一种高度保守的 microRNA，如果发生突变，会导致人类和小鼠耳聋。尽管 miR-1271 和 miR-96 的序列略有不同，但我们的体外实验表明它们具有相同的调节活性。我们已经从包括 GPHN、RGS2、HOMER1 和 KCC2 在内的脑表达基因中鉴定出 mRNAs，它们都具有相同的 miR-96 和 miR-1271 调节元件。有趣的是，人类 miR-1271 在脑组织中大量表达，而 miR-96 则没有高度表达。啮齿动物 miR-1271 的前体在其前体茎中含有几个序列差异，这些差异似乎降低了 microRNA 加工的效率。我们的数据表明，尽管 miR-1271 和 miR-96 在体外具有相同的功能，但它们在体内的功能在某种程度上是独特的。鉴于其表达模式和靶基因的性质，miR-1271 可能在调节人类神经发育或功能的某些方面具有重要的、尽管是非保守的作用。
