Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan, Metabolome Division, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Sanbancho 5, Chiyoda-ku, Tokyo 102-0075, Japan, Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachiouji-shi, Tokyo 192-0397, Japan, Department of Bioengineering, United Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan and Biomolecular Characterization Team, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Nucleic Acids Res. 2014 Feb;42(4):2708-24. doi: 10.1093/nar/gkt1271. Epub 2013 Dec 5.
The U1 small nuclear ribonucleoprotein (snRNP) plays pivotal roles in pre-mRNA splicing and in regulating mRNA length and isoform expression; however, the mechanism of U1 snRNA quality control remains undetermined. Here, we describe a novel surveillance pathway for U1 snRNP biogenesis. Mass spectrometry-based RNA analysis showed that a small population of SMN complexes contains truncated forms of U1 snRNA (U1-tfs) lacking the Sm-binding site and stem loop 4 but containing a 7-monomethylguanosine 5' cap and a methylated first adenosine base. U1-tfs form a unique SMN complex, are shunted to processing bodies and have a turnover rate faster than that of mature U1 snRNA. U1-tfs are formed partly from the transcripts of U1 genes and partly from those lacking the 3' box elements or having defective SL4 coding regions. We propose that U1 snRNP biogenesis is under strict quality control: U1 transcripts are surveyed at the 3'-terminal region and U1-tfs are diverted from the normal U1 snRNP biogenesis pathway.
U1 小核核糖核蛋白 (snRNP) 在 pre-mRNA 剪接以及调节 mRNA 长度和亚型表达方面发挥着关键作用；然而，U1 snRNA 的质量控制机制仍未确定。在这里，我们描述了 U1 snRNP 生物发生的一种新的监控途径。基于质谱的 RNA 分析表明，一小部分 SMN 复合物包含截短形式的 U1 snRNA（U1-tfs），它们缺乏 Sm 结合位点和茎环 4，但含有 7-单甲基鸟苷 5' 帽和甲基化的第一个腺苷碱基。U1-tfs 形成独特的 SMN 复合物，被分流到处理体中，其周转率比成熟的 U1 snRNA 更快。U1-tfs 的形成部分来自 U1 基因的转录本，部分来自那些缺乏 3' 框元件或具有缺陷 SL4 编码区的转录本。我们提出 U1 snRNP 的生物发生受到严格的质量控制：在 3' 末端区域对 U1 转录本进行检测，并且 U1-tfs 从正常的 U1 snRNP 生物发生途径中被转移。
