RT Journal Article
SR Electronic
T1 Nuclear poly(A) tail size is regulated by Cnot1 during the serum response
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 773432
DO 10.1101/773432
A1 Richa Singhania
A1 Graeme J. Thorn
A1 Kathryn Williams
A1 Raj D. Gandhi
A1 Clara Daher
A1 Adeline Barthet-Barateig
A1 Hannah N. Parker
A1 Wahyu Utami
A1 Mustafa Al-Siraj
A1 David A. Barrett
A1 Jonathan A.D. Wattis
A1 Cornelia H. de Moor
YR 2019
UL http://biorxiv.org/content/early/2019/09/19/773432.abstract
AB 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.