Principles of mRNA control by human PUM proteins elucidated from multimodal experiments and integrative data analysis

被引：12

作者：

Wolfe, Michael B. ^{[1
,2
,11
]}

Schagat, Trista L. ^{[3
]}

Paulsen, Michelle T. ^{[4
]}

Magnuson, Brian ^{[5
,6
]}

Ljungman, Mats ^{[4
,6
,7
,10
]}

Park, Daeyoon ^{[8
]}

Zhang, Chi ^{[9
]}

Campbell, Zachary T. ^{[9
]}

Goldstrohm, Aaron C. ^{[8
]}

Freddolino, Peter L. ^{[1
,2
]}

机构：

[1] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[3] Promega Corp, Fitchburg, WI 53711 USA

[4] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA

[7] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA

[8] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA

[9] Univ Texas Dallas, Dept Biol Sci, Richardson, TX 75080 USA

[10] Univ Michigan, Ctr RNA Biomed, Ann Arbor, MI 48109 USA

[11] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

来源：

RNA | 2020年 / 26卷 / 11期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

RNA decay; Pumilio; machine learning; BINDING-PROTEIN; TRANSLATIONAL REPRESSION; SEQUENCE SPECIFICITY; NONCODING RNA; PUMILIO; GENE; DNA; STABILITY; IDENTIFICATION; RECOGNITION;

D O I：

10.1261/rna.077362.120

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The human PUF-family proteins, PUM1 and PUM2, posttranscriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3'-UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady-state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic labeling to measure changes in RNA turnover in response to depletion of PUM1/2, showing that human PUM proteins regulate expression almost exclusively by changing RNA stability. We also applied an in vitro selection workflow to precisely identify the binding preferences of PUM1 and PUM2. By integrating our results with prior knowledge, we developed a "rulebook" of key contextual features that differentiate functional versus nonfunctional PREs, allowing us to train machine learning models that accurately predict the functional regulation of RNA targets by the human PUM proteins.

引用

页码：1680 / +

页数：29

共 105 条

[1] Predicting effective microRNA target sites in mammalian mRNAs [J].