Mammalian Pum1 and Pum2 Control Body Size via Translational Regulation of the Cell Cycle Inhibitor Cdkn1b

Cell Reports
Kaibo LinEugene Yujun Xu

Abstract

Body and organ size regulation in mammals involves multiple signaling pathways and remains largely enigmatic. Here, we report that Pum1 and Pum2, which encode highly conserved PUF RNA-binding proteins, regulate mouse body and organ size by post-transcriptional repression of the cell cycle inhibitor Cdkn1b. Binding of PUM1 or PUM2 to Pumilio binding elements (PBEs) in the 3' UTR of Cdkn1b inhibits translation, promoting G1-S transition and cell proliferation. Mice with null mutations in Pum1 and Pum2 exhibit gene dosage-dependent reductions in body and organ size, and deficiency for Cdkn1b partially rescues postnatal growth defects in Pum1-/- mice. We propose that coordinated tissue-specific expression of Pum1 and Pum2, which involves auto-regulatory and reciprocal post-transcriptional repression, contributes to the precise regulation of body and organ size. Hence PUM-mediated post-transcriptional control of cell cycle regulators represents an additional layer of control in the genetic regulation of organ and body size.

Citations

Mar 9, 2019·ELife·Filipa Carvalhal Marques, Igor Ulitsky
Jan 30, 2020·Cell Biology and Toxicology·Jin WangHao Zhou
Mar 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Katherine E UyhaziHaifan Lin
Jun 13, 2020·Frontiers in Bioengineering and Biotechnology·Shiqi ZhangYu-Dong Cai
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Xiaobo Wang, Ekaterina Voronina
Oct 1, 2020·Clinical and Translational Medicine·Di WangYunhui Liu
Dec 6, 2020·Pathogens·Chenrong WangQun Liu
Jan 7, 2021·Cancers·Maciej J SmialekJadwiga Jaruzelska
Jan 29, 2021·International Journal of Biological Macromolecules·Ravi GorSatish Ramalingam
May 19, 2021·The Journal of Obstetrics and Gynaecology Research·Peihong LinJianwen Ye
Aug 28, 2021·International Journal of Molecular Sciences·Rico SchieweckMichael A Kiebler
Sep 18, 2021·Journal of Biomedical Research·Xin LiEugene Yujun Xu

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Methods Mentioned

BETA
nuclear magnetic resonance
Fluorescence-activated cell sorting
immunoprecipitation
eCLIP
RIP
eCLIP-seq
Transgenic
genotyping
flow cytometry
Flow

Software Mentioned

GraphPad Prism
Excel
Flowjo
MODfit LT

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