ZSWIM8 destabilizes many murine microRNAs and is required for proper embryonic growth and development.
ZSWIM8 destabilizes many murine microRNAs and is required for proper embryonic growth and development.
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DOI：
10.1101/gr.278073.123
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发表时间：
2023-09
期刊：
影响因子：
7
通讯作者：
Bartel, David P.
中科院分区：
文献类型：
--
作者：
Shi, Charlie Y.;Elcavage, Lara E.;Chivukula, Raghu R.;Stefano, Joanna;Kleaveland, Benjamin;Bartel, David P.
微小RNA（miRNAs）与mRNA中的位点配对以指导这些RNA转录物的降解。相反，某些RNA转录物可以指导特定miRNA的降解。这种靶向的miRNA降解（TDMD）需要E3泛素连接酶。在这里，我们报告的功能，在小鼠胚胎中的WIM 8。Zswim 8 −/−胚胎比同窝出生的小，在出生时死亡。这种高度渗透性的围产期致死性显然是由肺泡上皮细胞成熟失败引起的肺囊状缺陷引起的。一些突变个体也有心脏室间隔缺损。这些发育异常伴随着在12种组织中观察到的超过50种miRNA的异常积累，这通常导致其mRNA靶点的抑制增强。这些对TDM 8敏感的miRNA优先从基因组miRNA簇产生，并且在某些情况下，TDM 8引起从miRNA发夹积累的优势链或同种型的转换-观察表明TDMD提供了一种将共同产生的miRNA彼此解偶联的机制。总体而言，我们的研究结果表明，在哺乳动物生物学中，TDMWIM 8和可能的TDMD的调节影响是广泛和重要的，并且证实了许多尚未鉴定的转录物的存在，这些转录物触发miRNA降解。
MicroRNAs (miRNAs) pair to sites in mRNAs to direct the degradation of these RNA transcripts. Conversely, certain RNA transcripts can direct the degradation of particular miRNAs. This target-directed miRNA degradation (TDMD) requires the ZSWIM8 E3 ubiquitin ligase. Here, we report the function of ZSWIM8 in the mouse embryo. Zswim8−/− embryos were smaller than their littermates and died near the time of birth. This highly penetrant perinatal lethality was apparently caused by a lung sacculation defect attributed to failed maturation of alveolar epithelial cells. Some mutant individuals also had heart ventricular septal defects. These developmental abnormalities were accompanied by aberrant accumulation of more than 50 miRNAs observed across 12 tissues, which often led to enhanced repression of their mRNA targets. These ZSWIM8-sensitive miRNAs were preferentially produced from genomic miRNA clusters, and in some cases, ZSWIM8 caused a switch in the dominant strand or isoform that accumulated from a miRNA hairpin—observations suggesting that TDMD provides a mechanism to uncouple coproduced miRNAs from each other. Overall, our findings indicate that the regulatory influence of ZSWIM8, and presumably TDMD, in mammalian biology is widespread and consequential, and posit the existence of many yet-unidentified transcripts that trigger miRNA degradation.
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影响因子：
64.5
作者：
Kleaveland B;Shi CY;Stefano J;Bartel DP
通讯作者：
Bartel DP
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
16
作者：
Eisen, Timothy J.;Eichhorn, Stephen W.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
16
作者：
Hutter, Katharina;Lohmueller, Michael;Herzog, Sebastian
通讯作者：
Herzog, Sebastian
影响因子：
8.8
作者：
Donnelly, Bridget F.;Yang, Bing;Grimme, Acadia L.;Vieux, Karl-Frederic;Liu, Chen-Yu;Zhou, Lecong;McJunkin, Katherine
通讯作者：
McJunkin, Katherine