NDLI: The role of context in RNA structure: flanking sequences reconfigure CAG motif folding in huntingtin exon 1 transcripts

Content Provider	PubMed Central
Author	Steven, Busan Weeks, Kevin M.
Abstract	The length of the CAG repeat region in the huntingtin messenger RNA is predictive of Huntington’s disease. Structural studies of CAG repeat-containing RNAs suggest that these sequences form simple hairpin structures; however, in the context of the full-length huntingtin mRNA, CAG repeats may form complex structures that could be targeted for therapeutic intervention. We examined the structures of transcripts spanning the first exon of the huntingtin mRNA with both healthy and disease-prone repeat lengths. In transcripts with 17 to 70 repeats, the CAG sequences base paired extensively with bases in the 5′ UTR and with a conserved region downstream of the CCG repeat region. In huntingtin transcripts with healthy numbers of repeats, the previously observed CAG hairpin was either absent or short. In contrast, in transcripts with disease-associated numbers of repeats, a CAG hairpin was present and extended from a three-helix junction. Our findings demonstrate the profound importance of sequence context in RNA folding and identify specific structural differences between healthy and disease-inducing huntingtin alleles that may be targets for therapeutic intervention.
Related Links	http://dx.doi.org/10.1021/bi401129r
Ending Page	8225
Page Count	7
Starting Page	8219
File Format	PDF
ISSN	00062960
e-ISSN	15204995
Journal	Biochemistry
Issue Number	46
Volume Number	52
Language	English
Publisher Date	2013-11-19
Access Restriction	Open
Subject Keyword	Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry

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

Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation

RNA-binding Protein TLS Is a Major Nuclear Aggregate-interacting Protein in Huntingtin Exon 1 with Expanded Polyglutamine-expressing Cells

RNA processing of beta-globin transcripts containing 5' flanking and structural gene sequences.

An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting

Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin

Does the mutant CAG expansion in huntingtin mRNAinterfere with exonucleolytic cleavage of its first exon?

The Interaction of Polyglutamine Peptides with Lipid Membranes Is Regulated by Flanking Sequences Associated with Huntingtin*

Huntingtin and Its Role in Mechanisms of RNA-Mediated Toxicity

Flanking sequences regulate the toxicity, non-ATG translation, and aggregation of RNA with tandem CAG Repeats

The role of context in RNA structure: flanking sequences reconfigure CAG motif folding in huntingtin exon 1 transcripts

Similar Documents

Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation

RNA-binding Protein TLS Is a Major Nuclear Aggregate-interacting Protein in Huntingtin Exon 1 with Expanded Polyglutamine-expressing Cells

RNA processing of beta-globin transcripts containing 5' flanking and structural gene sequences.

An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting

Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin

Does the mutant CAG expansion in huntingtin mRNAinterfere with exonucleolytic cleavage of its first exon?

The Interaction of Polyglutamine Peptides with Lipid Membranes Is Regulated by Flanking Sequences Associated with Huntingtin*

Huntingtin and Its Role in Mechanisms of RNA-Mediated Toxicity

Flanking sequences regulate the toxicity, non-ATG translation, and aggregation of RNA with tandem CAG Repeats

The role of context in RNA structure: flanking sequences reconfigure CAG motif folding in huntingtin exon 1 transcripts