Asset Details
Do you wish to reserve the book?
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
Do you wish to request the book?
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
2013
Overview
This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.
Function of Perlman syndrome exonuclease
The Lin28-let-7 signalling cascade has been linked to stem cell function, cancers and various aspects of cellular metabolism. The pluripotency factor Lin28 recruits the 3′ terminal uridylyl transferases that add an oligouridine tail to let-7 precursor RNA. Here Richard Gregory and colleagues demonstrate that Dis3l2, a protein mutated in Perlman syndrome of fetal overgrowth and predisposition to Wilms' tumour, is the exonuclease that mediates the degradation of uridylated pre-let-7 in mouse embryonic stem cells. The identification of a decay pathway for uridylated RNAs raises the possibility that this type of post-transcriptional regulation might occur more widely.
The pluripotency factor Lin28 blocks the expression of let-7 microRNAs in undifferentiated cells during development, and functions as an oncogene in a subset of cancers
1
. Lin28 binds to let-7 precursor (pre-let-7) RNAs and recruits 3′ terminal uridylyl transferases to selectively inhibit let-7 biogenesis
2
,
3
,
4
. Uridylated pre-let-7 is refractory to processing by Dicer, and is rapidly degraded by an unknown RNase
5
. Here we identify Dis3l2 as the 3′–5′ exonuclease responsible for the decay of uridylated pre-let-7 in mouse embryonic stem cells. Biochemical reconstitution assays show that 3′ oligouridylation stimulates Dis3l2 activity
in vitro
, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7. Our study establishes 3′ oligouridylation as an RNA decay signal for Dis3l2, and identifies the first physiological RNA substrate of this new exonuclease, which is mutated in the Perlman syndrome of fetal overgrowth and causes a predisposition to Wilms’ tumour development
6
.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Cloning
/ Decay
/ Embryonic Stem Cells - metabolism
/ Exoribonucleases - metabolism
/ Fetal Macrosomia - enzymology
/ Fetal Macrosomia - metabolism
/ Humanities and Social Sciences
/ Humans
/ letter
/ Mice
/ Proteins
/ RNA Processing, Post-Transcriptional
/ RNA-Binding Proteins - metabolism
/ Science
/ Uridine Monophosphate - analogs & derivatives
