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Nuclear poly(A) tail size is regulated by Cnot1 during the serum response

Singhania, Richa; Thorn, Graeme J.; Williams, Kathryn; Gandhi, Raj D.; Daher, Clara; Barthet-Barateig, Adeline; Parker, Hannah N.; Utami, Wahyu; Al-Siraj, Mustafa; Barrett, David A.; Wattis, Jonathan A.D.; de Moor, Cornelia H.

Authors

Richa Singhania

Graeme J. Thorn

Kathryn Williams

Raj D. Gandhi

Clara Daher

Adeline Barthet-Barateig

Hannah N. Parker

Wahyu Utami

Mustafa Al-Siraj

David A. Barrett



Abstract

The poly(A) tail removal from mRNAs introduces a delay between mRNA synthesis and decay. We measured levels and poly(A) tail sizes of serum-induced mRNAs and used mathematical modelling to compare their deadenylation time with the delay in decay and found that they are indeed correlated. Discrepancies between our data and the polyadenylation models at later time points after the peak of induction led us to investigate the size of the poly(A) tails on newly made mRNA. Surprisingly, new serum-induced mRNAs synthesised late in induction had short poly(A) tails (around A25) in the nucleus. In addition, newly made constitutive mRNAs had medium sized poly(A) tails (around A50). To see if deadenylation was responsible for the new short poly(A) tails, we depleted Cnot1, a subunit of the CCR4/NOT deadenylase. Cnot1 depletion led to slower deadenylation of cytoplasmic mRNAs, as expected, but also decreased transcription and led to longer nuclear mRNA poly(A) tails. These observations implicate CCR4/NOT in regulating both the transcription and the nuclear poly(A) tail size of serum-induced mRNAs. Detection of some chromatin-associated mRNAs with long poly(A) tails suggested that nuclear deadenylation is an early event. Our data show that initial poly(A) tail size of mRNAs can be regulated and is not always 200-250 nucleotides, adding a novel layer to the control of gene expression.

Citation

Singhania, R., Thorn, G. J., Williams, K., Gandhi, R. D., Daher, C., Barthet-Barateig, A., …de Moor, C. H. (2019). Nuclear poly(A) tail size is regulated by Cnot1 during the serum response

Other Type Other
Acceptance Date Sep 19, 2019
Online Publication Date Sep 19, 2019
Publication Date Sep 19, 2019
Deposit Date Jan 2, 2020
Publicly Available Date
DOI https://doi.org/10.1101/773432
Public URL https://nottingham-repository.worktribe.com/output/3018754
Related Public URLs https://www.biorxiv.org/content/10.1101/773432v1
Additional Information Preprint.