The developmentally timed decay of an essential microRNA family is seed-sequence dependent.

The developmentally timed decay of an essential microRNA family is seed-sequence dependent.
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DOI:
10.1016/j.celrep.2022.111154
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发表时间:
2022-08-09
期刊:
影响因子:
8.8
通讯作者:
McJunkin, Katherine
McJunkin, Katherine
中科院分区:
生物学1区
文献类型:
--
作者:
Donnelly, Bridget F.;Yang, Bing;Grimme, Acadia L.;Vieux, Karl-Frederic;Liu, Chen-Yu;Zhou, Lecong;McJunkin, Katherine

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MicroRNA (miRNA)的丰度受到生物发生和衰变的严格控制。在这里,我们表明,在秀丽隐杆线虫从胚胎到幼虫发育的过渡过程中,mir-35 miRNA家族经历了选择性衰变。miRNA的种子序列对于这种调控是必要的,并且在很大程度上是充分的。种子外的序列(3 '端)调节胚胎中mir-35的丰度,但在向幼虫发育过渡的急剧衰变中不是必需的。miRNA 3’端的酶修饰既不普遍,也与衰变的变化无关,这表明miRNA 3’端显示不是该机制的核心特征,并进一步支持种子驱动的衰变模型。我们的研究结果表明,种子序列特异性衰变可以选择性和一致性地调节miRNA种子家族的所有冗余成员,这类机制在动态调节miRNA家族的靶库方面具有巨大的生物学和治疗潜力。Donnelly等人表明,序列特异性miRNA衰减有助于miRNA库在发育过程中的动态变化。mir-35家族的种子序列在胚胎发生结束时驱动这些miRNA的衰变,这表明一种选择性衰变机制可以共同调节miRNA家族的所有冗余成员。
MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here, we show that the mir-35 miRNA family undergoes selective decay at the transition from embryonic to larval development in C. elegans. The seed sequence of the miRNA is necessary and largely sufficient for this regulation. Sequences outside the seed (3′ end) regulate mir-35 abundance in the embryo but are not necessary for sharp decay at the transition to larval development. Enzymatic modifications of the miRNA 3′ end are neither prevalent nor correlated with changes in decay, suggesting that miRNA 3′ end display is not a core feature of this mechanism and further supporting a seed-driven decay model. Our findings demonstrate that seed-sequence-specific decay can selectively and coherently regulate all redundant members of a miRNA seed family, a class of mechanism that has great biological and therapeutic potential for dynamic regulation of a miRNA family’s target repertoire. Donnelly et al. show that sequence-specific miRNA decay contributes to the dynamic changes in miRNA repertoire during development. The seed sequence of the mir-35 family drives decay of these miRNAs at the end of embryogenesis, suggesting a selective decay mechanism that can co-regulate all redundant members of a miRNA family.
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