C2H2-zinc-finger transcription factors bind RNA and function in diverse post-transcriptional regulatory processes

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cell Pub Date : 2024-09-19 DOI:10.1016/j.molcel.2024.08.037
Syed Nabeel-Shah, Shuye Pu, James D. Burns, Ulrich Braunschweig, Nujhat Ahmed, Giovanni L. Burke, Hyunmin Lee, Ernest Radovani, Guoqing Zhong, Hua Tang, Edyta Marcon, Zhaolei Zhang, Timothy R. Hughes, Benjamin J. Blencowe, Jack F. Greenblatt
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Abstract

Cys2-His2 zinc-finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs) yet remain largely uncharacterized. Although certain family members, e.g., GTF3A, have been shown to bind both DNA and RNA, the extent to which C2H2-ZNFs interact with—and regulate—RNA-associated processes is not known. Using UV crosslinking and immunoprecipitation (CLIP), we observe that 148 of 150 analyzed C2H2-ZNFs bind directly to RNA in human cells. By integrating CLIP sequencing (CLIP-seq) RNA-binding maps for 50 of these C2H2-ZNFs with data from chromatin immunoprecipitation sequencing (ChIP-seq), protein-protein interaction assays, and transcriptome profiling experiments, we observe that the RNA-binding profiles of C2H2-ZNFs are generally distinct from their DNA-binding preferences and that they regulate a variety of post-transcriptional processes, including pre-mRNA splicing, cleavage and polyadenylation, and m6A modification of mRNA. Our results thus define a substantially expanded repertoire of C2H2-ZNFs that bind RNA and provide an important resource for elucidating post-transcriptional regulatory programs.

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C2H2-锌指转录因子与 RNA 结合并在多种转录后调控过程中发挥作用
Cys2-His2锌指蛋白(C2H2-ZNFs)构成了 DNA 结合转录因子(TFs)中最大的一类,但大部分尚未定性。虽然某些家族成员(如 GTF3A)已被证明能同时结合 DNA 和 RNA,但 C2H2-ZNFs 与 RNA 相关过程的相互作用和调控程度尚不清楚。利用紫外交联和免疫沉淀(CLIP)技术,我们观察到 150 个被分析的 C2H2-ZNFs 中有 148 个直接与人体细胞中的 RNA 结合。通过将其中 50 个 C2H2-ZNFs 的 CLIP 测序(CLIP-seq)RNA 结合图谱与染色质免疫沉淀测序(ChIP-seq)、蛋白质-蛋白质相互作用测定和转录组图谱分析实验的数据进行整合、我们观察到,C2H2-ZNFs 的 RNA 结合特征通常不同于它们的 DNA 结合偏好,而且它们能调控多种转录后过程,包括 mRNA 的前剪接、裂解和多聚腺苷酸化,以及 mRNA 的 m6A 修饰。因此,我们的研究结果确定了可与 RNA 结合的 C2H2-ZNFs 种类,为阐明转录后调控程序提供了重要资源。
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来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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