Unknown

Dataset Information

0

Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells.


ABSTRACT: Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH)2D target gene CYP24A1 involved immunoprecipitation of hnRNPC1/C2 with CYP24A1 chromatin and RNA. Knockdown of hnRNPC1/C2 suppressed expression of CYP24A1, but also increased expression of an exon 10-skipped CYP24A1 splice variant; in a minigene model the latter was attenuated by a functional VDRE in the CYP24A1 promoter. In genome-wide analyses, knockdown of hnRNPC1/C2 resulted in 3500 differentially expressed genes and 2232 differentially spliced genes, with significant commonality between groups. 1,25(OH)2D induced 324 differentially expressed genes, with 187 also observed following hnRNPC1/C2 knockdown, and a further 168 unique to hnRNPC1/C2 knockdown. However, 1,25(OH)2D induced only 10 differentially spliced genes, with no overlap with differentially expressed genes. These data indicate that hnRNPC1/C2 binds to both DNA and RNA and influences both gene expression and RNA splicing, but these actions do not appear to be linked through 1,25(OH)2D-mediated induction of transcription.

SUBMITTER: Zhou R 

PROVIDER: S-EPMC5314791 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells.

Zhou Rui R   Park Juw Won JW   Chun Rene F RF   Lisse Thomas S TS   Garcia Alejandro J AJ   Zavala Kathryn K   Sea Jessica L JL   Lu Zhi-Xiang ZX   Xu Jianzhong J   Adams John S JS   Xing Yi Y   Hewison Martin M  

Nucleic acids research 20160926 2


Traditionally recognized as an RNA splicing regulator, heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) can also bind to double-stranded DNA and function in trans as a vitamin D response element (VDRE)-binding protein. As such, hnRNPC1/C2 may couple transcription induced by the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)<sub>2</sub>D) with subsequent RNA splicing. In MG63 osteoblastic cells, increased expression of the 1,25(OH)<sub>2</sub>D target gene CYP24A1 involved  ...[more]

Similar Datasets

2016-12-06 | GSE63086 | GEO
| S-EPMC4261231 | biostudies-literature
| S-EPMC3457347 | biostudies-literature
| S-EPMC1257739 | biostudies-literature
| S-EPMC17817 | biostudies-literature
| S-EPMC1186688 | biostudies-other
| S-EPMC4473559 | biostudies-literature
| S-EPMC2791692 | biostudies-literature
| S-EPMC140676 | biostudies-literature
| S-EPMC4414404 | biostudies-literature