TRMP, a p53-inducible long noncoding RNA, regulates G1/S cell cycle progression by modulating IRES-dependent p27 translation

Cell Death & Disease
Yang YangYide Mei

Abstract

The tumor suppressor p53 plays a pivotal role in the protection against cancer. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an important role in the regulation of the p53 pathway, however, the detailed mechanisms remain to be further elucidated. In this study, we report a new p53-inducible lncRNA that we termed TRMP (TP53-regulated modulator of p27). As a direct transcriptional target of p53, TRMP plays an unexpected pro-survival function. Knockdown of TRMP inhibits cell proliferation by inducing a G1 cell cycle arrest. Mechanistically, TRMP suppresses internal ribosomal entry site (IRES)-dependent translation of p27 by competing p27 mRNA for polypyrimidine tract-binding protein 1 (PTBP1) binding. Furthermore, TRMP is able to regulate cell proliferation, G1/S cell cycle progression, and tumor xenograft growth via the inhibition of p27. Taken together, these findings suggest lncRNA as a new layer to fine-tune the p53 response and reveal TRMP as an important downstream effector of p53 activity.

References

May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Dec 1, 2000·Nature·B VogelsteinA J Levine
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Dec 5, 2002·Genes & Development·Michael KullmannLudger Hengst
Nov 9, 2004·Nature Cell Biology·Takumi KamuraKeiichi I Nakayama
Sep 24, 2005·Science·Florian C OberstrassFrédéric H-T Allain
Oct 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Satyajit K KarnikSeung K Kim
Nov 8, 2007·Cell Cycle·Carlos le SageReuven Agami
Mar 21, 2008·Nature Reviews. Cancer·Isabel M ChuJoyce M Slingerland
May 6, 2008·Nature Cell Biology·Ezgi TasdemirGuido Kroemer
May 5, 2009·Cell·Karen H Vousden, Carol Prives
Sep 20, 2011·Molecular Cell·Kevin C Wang, Howard Y Chang
Nov 24, 2011·The Journal of Biological Chemistry·Anthony M BarsottiCarol Prives
Jun 21, 2012·Genes & Development·William A Freed-Pastor, Carol Prives
Nov 28, 2012·Journal of Molecular Biology·Je-Hyun YoonMyriam Gorospe
Apr 6, 2013·Nucleic Acids Research·Qian LiuYin-Yuan Mo
Jan 1, 2014·Cancer Letters·Juan LiuZhaohui Feng
Apr 12, 2014·Journal of Molecular Cell Biology·Ali ZhangYin-Yuan Mo
Jul 22, 2015·Biochimica Et Biophysica Acta·Elena GrossiMaite Huarte
Aug 19, 2015·The International Journal of Biochemistry & Cell Biology·Su Su Thae HnitQihan Dong
Sep 29, 2015·EMBO Reports·Vivek SharmaTom Misteli
Nov 6, 2015·Nature Medicine·Maite Huarte
Apr 3, 2016·Cold Spring Harbor Perspectives in Medicine·Eileen White
Apr 14, 2016·Cancer Cell·Adam M Schmitt, Howard Y Chang
Jul 3, 2016·Cold Spring Harbor Perspectives in Medicine·Timothy J Humpton, Karen H Vousden
Jul 5, 2016·Advances in Experimental Medicine and Biology·Yide Mei, Mian Wu
Jul 15, 2016·Cold Spring Harbor Perspectives in Medicine·Yael Aylon, Moshe Oren

❮ Previous
Next ❯

Citations

Jul 3, 2019·Proceedings of the National Academy of Sciences of the United States of America·Chenfeng WangYide Mei
May 21, 2020·RNA Biology·Abhinav K Jain
Aug 15, 2020·Frontiers in Genetics·Manuel Flores-Concha, Ángel A Oñate
Mar 3, 2020·Journal of Zhejiang University. Science. B·Wei ZhuCai-Ping Ren
Feb 23, 2019·International Journal of Molecular Sciences·Anne-Claire GodetAnne-Catherine Prats
Oct 30, 2019·Molecular Therapy Oncolytics·Da-Fang ZhengYi-Sheng Tao
Feb 19, 2021·Signal Transduction and Targeted Therapy·Ping SongXian Wang
Jun 8, 2021·Molecular Therapy. Nucleic Acids·Tian ShuaiFengmin Shao
Apr 28, 2021·Chemical Biology & Drug Design·Masomeh MalekiBahman Yousefi
Sep 15, 2020·Seminars in Cancer Biology·Song ChenLianxin Liu
Dec 11, 2021·Briefings in Bioinformatics·Eun-Gyeong ParkJin-Wu Nam
Jan 14, 2022·Proceedings of the National Academy of Sciences of the United States of America·Chenfeng WangYide Mei

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
immunoprecipitation
ChIP
flow cytometry
pull-down
pull-downed
pull down
xenografts
PCR
Assay

Software Mentioned

Excel
ImageJ
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.