Eshelman School of Pharmacy and Renaissance Computing Institute, University of North Carolina at Chapel Hill, NC, USA.
BMC Bioinformatics. 2010 Dec 20;11:602. doi: 10.1186/1471-2105-11-602.
Small RNAs are known to regulate diverse gene expression processes including translation, transcription, and splicing. Among small RNAs, the microRNAs (miRNAs) of 17 to 27 nucleotides (nts) undergo biogeneses including primary transcription, RNA excision and folding, nuclear export, cytoplasmic processing, and then bioactivity as regulatory agents. We propose that analogous hairpins from RNA molecules that function as part of the spliceosome might also be the source of small, regulatory RNAs (somewhat smaller than miRNAs).
Deep sequencing technology has enabled discovery of a novel 16-nt RNA sequence in total RNA from human brain that we propose is derived from RNU1, an RNA component of spliceosome assembly. Bioinformatic alignments compel inquiring whether the novel 16-nt sequence or its precursor have a regulatory function as well as determining aspects of how processing intersects with the miRNA biogenesis pathway. Specifically, our preliminary in silico investigations reveal the sequence could regulate splicing factor Arg/Ser rich 1 (SFRS1), a gene coding an essential protein component of the spliceosome. All 16-base source sequences in the UCSC Human Genome Browser are within the 14 instances of RNU1 genes listed in wgEncodeGencodeAutoV3. Furthermore, 10 of the 14 instances of the sequence are also within a common 28-nt hairpin-forming subsequence of RNU1.
An abundant 16-nt RNA sequence is sourced from a spliceosomal RNA, lies in a stem of a predicted RNA hairpin, and includes reverse complements of subsequences of the 3'UTR of a gene coding for a spliceosome protein. Thus RNU1 could function both as a component of spliceosome assembly and as inhibitor of production of the essential, spliceosome protein coded by SFRS1. Beyond this example, a general procedure is needed for systematic discovery of multiple alignments of sequencing, splicing, and RNA folding data.
已知小 RNA 可调节多种基因表达过程，包括翻译、转录和剪接。在小 RNA 中，17 至 27 个核苷酸（nt）的 microRNAs（miRNAs）经历生物发生，包括初级转录、RNA 切除和折叠、核输出、细胞质加工，然后作为调节因子发挥生物活性。我们提出，作为剪接体一部分发挥作用的 RNA 分子的类似发夹也可能是小调节 RNA（比 miRNAs 稍小）的来源。
深度测序技术使我们能够在人脑总 RNA 中发现一种新的 16-nt RNA 序列，我们提出该序列源自 RNU1，这是剪接体组装的 RNA 成分。生物信息学比对迫使我们询问该新的 16-nt 序列或其前体是否具有调节功能，以及确定加工与 miRNA 生物发生途径交叉的各个方面。具体而言，我们的初步计算机研究表明，该序列可能调节剪接因子 Arg/Ser 富含 1（SFRS1），这是剪接体的必需蛋白质成分编码基因。UCSC 人类基因组浏览器中的所有 16 碱基源序列都在 wgEncodeGencodeAutoV3 列出的 14 个 RNU1 基因实例中。此外，序列的 10 个实例也在 RNU1 的一个常见 28-nt 发夹形成亚序列中。
丰富的 16-nt RNA 序列源自剪接体 RNA，位于预测 RNA 发夹的茎中，并且包含编码剪接体蛋白基因 3'UTR 的亚序列的反向互补序列。因此，RNU1 可以作为剪接体组装的组成部分和 SFRS1 编码的必需剪接体蛋白产生的抑制剂发挥作用。除了这个例子之外，还需要一种系统的方法来进行测序、剪接和 RNA 折叠数据的多重比对的发现。
