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Title: Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis

Journal Article · · Nature Structural & Molecular Biology
DOI:https://doi.org/10.1038/nsmb.3428· OSTI ID:1409573

The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins to favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
DOE Contract Number:
SC0012704
OSTI ID:
1409573
Report Number(s):
BNL-114625-2017-JA¿¿¿
Journal Information:
Nature Structural & Molecular Biology, Vol. 24, Issue 8; ISSN 1545-9993
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

References (35)

Molecular Basis for Interaction of let-7 MicroRNAs with Lin28 journal November 2011
Selective Blockade of MicroRNA Processing by Lin28 journal April 2008
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway journal April 2013
Uridylation of miRNAs by HEN1 SUPPRESSOR1 in Arabidopsis journal April 2012
The Arabidopsis Nucleotidyl Transferase HESO1 Uridylates Unmethylated Small RNAs to Trigger Their Degradation journal April 2012
Refinement of Macromolecular Structures by the Maximum-Likelihood Method journal May 1997
Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells journal August 2009
Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard journal December 2007
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells journal December 2007
Lin28 sustains early renal progenitors and induces Wilms tumor journal April 2014
RNA Editing TUTase 1: structural foundation of substrate recognition, complex interactions and drug targeting journal October 2016
Uridylation by TUT4 and TUT7 Marks mRNA for Degradation journal December 2014
A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment journal July 2008
Target RNA-Directed Trimming and Tailing of Small Silencing RNAs journal June 2010
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids journal May 2007
Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing journal June 2008
let-7 microRNAs in development, stem cells and cancer journal September 2008
An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation journal November 2009
TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation journal August 2009
XDS journal January 2010
Structure and function of the polymerase core of TRAMP, a RNA surveillance complex journal August 2010
Coot model-building tools for molecular graphics journal November 2004
Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7) journal August 2012
Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3 journal June 2015
Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs journal October 2013
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs journal October 2012
Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility journal February 2012
Data processing and analysis with the autoPROC toolbox journal March 2011
Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA journal October 2008
RAS Is Regulated by the let-7 MicroRNA Family journal March 2005
Single‐molecule approach to immunoprecipitated protein complexes: insights into miRNA uridylation journal June 2011
TUT 7 controls the fate of precursor micro RNA s by using three different uridylation mechanisms journal May 2015
Phaser crystallographic software journal July 2007
Lin28 promotes transformation and is associated with advanced human malignancies journal May 2009

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