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

Research output: Contribution to journalArticlepeer-review


  • Rui Zhou
  • Juw Won Park
  • Rene Chun
  • Thomas Lisse
  • Alejandro J Garcia
  • Kathryn Zavala
  • Jessica Sea
  • Zhi-xiang Lu
  • Jianzhong Xu
  • John Adams
  • Yi Xing

Colleges, School and Institutes

External organisations

  • UCLA Orthoped Hosp
  • University of California
  • The Jackson Laboratory, Bar Harbor, ME 04609, USA
  • Department of Orthopaedics, The Orthopedic Surgery Center of Chinese PLA, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China


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.


Original languageEnglish
Pages (from-to)606–618
Number of pages13
JournalNucleic Acids Research
Issue number2
Early online date26 Sep 2016
Publication statusPublished - Jan 2017