PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes

61Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Alternative splicing of competing 5′ splice sites is regulated by enhancers and silencers in the spliced exon. We have characterized sequences and splicing factors that regulate alternative splicing of PLP and DM20, myelin proteins produced by oligodendrocytes (OLs) by selection of 5′ splice sites in exon 3. We identify a G-rich enhancer (M2) of DM20 5′ splice site in exon 3B and show that individual G triplets forming M2 are functionally distinct and the distal group plays a dominant role. G-rich M2 and a G-rich splicing enhancer (ISE) in intron 3 share similarities in function and protein binding. The G-rich sequences are necessary for binding of hnRNPs to both enhancers. Reduction in hnRNPH and F expression in differentiated OLs correlates temporally with increased PLP/DM20 ratio. Knock down of hnRNPH increased PLP/DM20 ratio, while hnRNPF did not. Silencing hnRNPH and F increased the PLP/DM20 ratio more than hnRNPH alone, demonstrating a novel synergistic effect. Mutation of M2, but not ISE reduced the synergistic effect. Replacement of M2 and all G runs in exon 3B abolished it almost completely. We conclude that developmental changes in hnRNPH/F associated with OLs differentiation synergistically regulate PLP alternative splicing and a G-rich enhancer participates in the regulation. © 2007 The Author(s).

References Powered by Scopus

Understanding alternative splicing: Towards a cellular code

1040Citations
N/AReaders
Get full text

Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss

441Citations
N/AReaders
Get full text

Alternative RNA splicing in the nervous system

289Citations
N/AReaders
Get full text

Cited by Powered by Scopus

G-quadruplexes in RNA biology

245Citations
N/AReaders
Get full text

Argonaute proteins couple chromatin silencing to alternative splicing

227Citations
N/AReaders
Get full text

Genetic Control of Expression and Splicing in Developing Human Brain Informs Disease Mechanisms

153Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Wang, E., Dimova, N., & Cambi, F. (2007). PLP/DM20 ratio is regulated by hnRNPH and F and a novel G-rich enhancer in oligodendrocytes. Nucleic Acids Research, 35(12), 4164–4178. https://doi.org/10.1093/nar/gkm387

Readers over time

‘10‘11‘12‘13‘14‘15‘16‘17‘18‘19‘21‘22‘23‘24‘2502468

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 18

64%

Researcher 7

25%

Professor / Associate Prof. 3

11%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 18

69%

Biochemistry, Genetics and Molecular Bi... 5

19%

Chemistry 2

8%

Pharmacology, Toxicology and Pharmaceut... 1

4%

Save time finding and organizing research with Mendeley

Sign up for free
0