NDLI: Mechanism of Dis3L2 substrate recognition in the Lin28/let-7 pathway

Content Provider	PubMed Central
Author	Faehnle, Christopher R. Jack, Walleshauser Joshua-tor, Leemor
Abstract	The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs 1–4 . Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development 5 , glucose metabolism 6 and tissue regeneration 7 . Alternatively, Lin28 overexpression is correlated with the onset of numerous cancers 8 , while let-7, a tumor suppressor, silences several human oncogenes 5 . Lin28 binds to precursor let-7 (pre-let-7) hairpins 9 , triggering the 3' oligo-uridylation activity of TUT4/7 10–12 . The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3L2 13,14 , a homolog of the catalytic subunit of the RNA exosome. The molecular basis of Lin28 mediated recruitment of TUT4/7 to pre-let-7 and its subsequent degradation by Dis3L2 is largely unknown. To examine the mechanism of Dis3L2 substrate recognition we determined the structure of mouse Dis3L2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first twelve nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3L2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28/let-7 pathway.
Related Links	http://dx.doi.org/10.1038/nature13553
Ending Page	256
Page Count	5
Starting Page	252
File Format	PDF
ISSN	14764687
e-ISSN	14764687
Journal	Nature
Issue Number	7521
Volume Number	514
Language	English
Publisher Date	2014-10-09
Access Restriction	Open
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway

Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28

SOX2–LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors

3′ RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease

The Wnt–β-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancer stem cell expansion

The LIN28/let-7 Pathway in Cancer

Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs

Lin28 Mediates Radiation Resistance of Breast Cancer Cells via Regulation of Caspase, H2A.X and Let-7 Signaling

The Lin28 cold-shock domain remodels pre-let-7 microRNA

Mechanism of Dis3L2 substrate recognition in the Lin28/let-7 pathway

Similar Documents

A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway

Bistable Switch in let-7 miRNA Biogenesis Pathway Involving Lin28

SOX2–LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors

3′ RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease

The Wnt–β-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancer stem cell expansion

The LIN28/let-7 Pathway in Cancer

Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs

Lin28 Mediates Radiation Resistance of Breast Cancer Cells via Regulation of Caspase, H2A.X and Let-7 Signaling

The Lin28 cold-shock domain remodels pre-let-7 microRNA

Mechanism of Dis3L2 substrate recognition in the Lin28/let-7 pathway