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小分子 ORF 作为 和 中 pri-miRNAs 和 miRNAs 表达的新调控因子。

Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in and .

机构信息

Molecular, Cellular and Developmental Biology Department (MCD), Centre de Biologie Integrative (CBI), University of Toulouse, CNRS, UPS, 31062 Toulouse, France.

Laboratoire de Recherche en Sciences Végétales, UMR5546 CNRS, UPS Université de Toulouse, INP, 31320 Auzeville-Tolosan, France.

出版信息

Int J Mol Sci. 2022 May 20;23(10):5764. doi: 10.3390/ijms23105764.

DOI:10.3390/ijms23105764
PMID:35628573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9144653/
Abstract

MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in pri-miRNAs annotated as long non-coding RNAs (lncRNAs) and defined as MIRHGs (for miRNA Host Genes). However, several lnc pri-miRNAs contain translatable small open reading frames (smORFs). If smORFs present within lncRNAs can encode functional small peptides, they can also constitute -regulatory elements involved in lncRNA decay. Here, we investigated the possible involvement of smORFs in the regulation of lnc pri-miRNAs in and , focusing on pri-miRNAs previously shown to contain translatable smORFs. We show that smORFs regulate the expression levels of pri-miR-155 and pri-miR-497, and pri-miR-8 and pri-miR-14, and also affect the expression and activity of their associated miRNAs. This smORF-dependent regulation is independent of the nucleotidic and amino acidic sequences of the smORFs and is sensitive to the ribosome-stalling drug cycloheximide, suggesting the involvement of translational events. This study identifies smORFs as new -acting elements involved in the regulation of pri-miRNAs and miRNAs expression, in both and .

摘要

MicroRNAs (miRNAs) 是小型调控性非编码 RNA，由 Microprocessor 复合物在细胞核中从长初级转录物 (pri-miRNAs) 切割产生前体 (pre-miRNAs)，然后将其输出到细胞质中并加工成熟 miRNA。一些 miRNA 位于被注释为长非编码 RNA (lncRNA) 的 pri-miRNA 中，被定义为 MIRHGs（miRNA 宿主基因）。然而，一些 lnc pri-miRNA 含有可翻译的小开放阅读框 (smORFs)。如果 lncRNA 中的 smORFs 能够编码功能性小肽，它们也可以构成参与 lncRNA 降解的调节元件。在这里，我们研究了 smORFs 参与 和 中 lnc pri-miRNA 调节的可能，重点研究了先前显示含有可翻译 smORFs 的 pri-miRNA。我们表明，smORFs 调节 pri-miR-155 和 pri-miR-497 以及 pri-miR-8 和 pri-miR-14 的表达水平，并且还影响它们相关 miRNA 的表达和活性。这种 smORF 依赖性调节独立于 smORFs 的核苷酸和氨基酸序列，并且对核糖体停滞药物环己酰亚胺敏感，表明涉及翻译事件。这项研究确定了 smORFs 作为参与 pri-miRNA 和 miRNA 表达调控的新的 - 作用元件，在 和 中均如此。

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