Identification of protein/mRNA network involving the PSORS1 locus gene CCHCR1 and the PSORS4 locus gene HAX1

Exp Cell Res. 2021 Feb 15;399(2):112471. doi: 10.1016/j.yexcr.2021.112471. Epub 2021 Jan 5.

Abstract

CCHCR1 (Coiled-Coil alpha-Helical Rod 1), maps to chromosomal region 6p21.3, within the major psoriasis susceptibility locus PSORS1. CCHCR1 itself is a plausible psoriasis candidate gene, however its role in psoriasis pathogenesis remains unclear. We previously demonstrated that CCHCR1 protein acts as a cytoplasmic docking site for RNA polymerase II core subunit 3 (RPB3) in cycling cells, suggesting a role for CCHCR1 in vesicular trafficking between cellular compartments. Here, we report a novel interaction between CCHCR1 and the RNA binding protein HAX1. HAX1 maps to chromosomal region 1q21.3 within the PSORS4 locus and is over-expressed in psoriasis. Both CCHCR1 and HAX1 share subcellular co-localization with mitochondria, nuclei and cytoplasmic vesicles as P-bodies. By a series of ribonucleoprotein immunoprecipitation (RIP) assays, we isolated a pool of mRNAs complexed with HAX1 and/or CCHCR1 proteins. Among the mRNAs complexed with both CCHCR1 and HAX1 proteins, there are Vimentin mRNA, previously described to be bound by HAX1, and CAMP/LL37 mRNA, whose gene product is over-expressed in psoriasis.

Keywords: CCHCR1; HAX1; LL37; Psoriasis; RNA metabolism; Vesicular trafficking; Vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cells, Cultured
  • Gene Regulatory Networks* / genetics
  • Genetic Loci
  • Genetic Predisposition to Disease / genetics
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Protein Interaction Maps* / genetics
  • Psoriasis / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits

Substances

  • Adaptor Proteins, Signal Transducing
  • CCHCR1 protein, human
  • HAX1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger