Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Genome Res. 2013 Feb;23(2):281-91. doi: 10.1101/gr.142968.112. Epub 2012 Oct 15.
Human U1 small nuclear (sn)RNA, required for splicing of pre-mRNA, is encoded by genes on chromosome 1 (1p36). Imperfect copies of these U1 snRNA genes, also located on chromosome 1 (1q12-21), were thought to be pseudogenes. However, many of these "variant" (v)U1 snRNA genes produce fully processed transcripts. Using antisense oligonucleotides to block the activity of a specific vU1 snRNA in HeLa cells, we have identified global transcriptome changes following interrogation of the Affymetrix Human Exon ST 1.0 array. Our results indicate that this vU1 snRNA regulates expression of a subset of target genes at the level of pre-mRNA processing. This is the first indication that variant U1 snRNAs have a biological function in vivo. Furthermore, some vU1 snRNAs are packaged into unique ribonucleoproteins (RNPs), and many vU1 snRNA genes are differentially expressed in human embryonic stem cells (hESCs) and HeLa cells, suggesting developmental control of RNA processing through expression of different sets of vU1 snRNPs.
人类 U1 小核 (sn)RNA 是剪接前体 mRNA 所必需的，由 1 号染色体（1p36）上的基因编码。这些 U1 snRNA 基因的不完全拷贝也位于 1 号染色体（1q12-21）上，被认为是假基因。然而，许多这些“变体”（v）U1 snRNA 基因产生完全加工的转录本。使用反义寡核苷酸阻断 HeLa 细胞中特定 vU1 snRNA 的活性，我们通过检测 Affymetrix Human Exon ST 1.0 阵列，鉴定了全局转录组变化。我们的结果表明，这种 vU1 snRNA 在 pre-mRNA 加工水平上调节一组靶基因的表达。这是第一个表明变体 U1 snRNA 在体内具有生物学功能的迹象。此外，一些 vU1 snRNA 被包装成独特的核糖核蛋白 (RNP)，并且许多 vU1 snRNA 基因在人胚胎干细胞 (hESC) 和 HeLa 细胞中的表达不同，这表明通过表达不同的 vU1 snRNP 来控制 RNA 加工的发育。
