Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May 7;78(3):434-444.e5.
doi: 10.1016/j.molcel.2020.03.022. Epub 2020 Apr 14.

Transcription Dynamics Regulate Poly(A) Tails and Expression of the RNA Degradation Machinery to Balance mRNA Levels

Boris Slobodin  1 , Anat Bahat  2 , Urmila Sehrawat  2 , Shirly Becker-Herman  3 , Binyamin Zuckerman  4 , Amanda N Weiss  2 , Ruiqi Han  5 , Ran Elkon  6 , Reuven Agami  5 , Igor Ulitsky  4 , Idit Shachar  3 , Rivka Dikstein  7
Affiliations
Free article

Transcription Dynamics Regulate Poly(A) Tails and Expression of the RNA Degradation Machinery to Balance mRNA Levels

Boris Slobodin et al. Mol Cell. .
Free article

Abstract

Gene expression is regulated by the rates of synthesis and degradation of mRNAs, but how these processes are coordinated is poorly understood. Here, we show that reduced transcription dynamics of specific genes leads to enhanced m6A deposition, preferential activity of the CCR4-Not complex, shortened poly(A) tails, and reduced stability of the respective mRNAs. These effects are also exerted by internal ribosome entry site (IRES) elements, which we found to be transcriptional pause sites. However, when transcription dynamics, and subsequently poly(A) tails, are globally altered, cells buffer mRNA levels by adjusting the expression of mRNA degradation machinery. Stress-provoked global impediment of transcription elongation leads to a dramatic inhibition of the mRNA degradation machinery and massive mRNA stabilization. Accordingly, globally enhanced transcription, such as following B cell activation or glucose stimulation, has the opposite effects. This study uncovers two molecular pathways that maintain balanced gene expression in mammalian cells by linking transcription to mRNA stability.

Keywords: CCR4-Not complex; IRES; RNA polymerase II; gene expression buffering; m(6)A; m6A methyltransferase complex; mRNA buffering; mRNA degradation; poly(A) tails; transcription.

PubMed Disclaimer

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources