Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex

Sci Rep. 2018 Mar 1;8(1):3832. doi: 10.1038/s41598-018-19427-6.

Abstract

The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes. Our analysis identifies 89 novel miRNA transcripts, 48 of which undergo Dicer-dependent biogenesis and are loaded onto the Argonaute silencing complex. Several of the identified mature miRNA and pre-miRNA transcripts are unique to specific MHC haplotypes and overlap common SNPs. Furthermore, 43 of the 89 identified novel miRNA transcripts lie within linkage disequilibrium blocks that contain a disease-associated SNP. These disease associated SNPs are associated with 65 unique disease phenotypes, suggesting that these transcripts may play a role in the etiology of numerous diseases associated with the MHC. Additional in silico analysis reveals the potential for thousands of putative pre-miRNA encoding loci within the MHC that may be expressed by different cell types and at different developmental stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / metabolism
  • Base Sequence
  • Cell Line
  • DEAD-box RNA Helicases / metabolism
  • HLA Antigens / genetics*
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Major Histocompatibility Complex / genetics*
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Ribonuclease III / metabolism
  • Sequence Analysis, RNA / methods

Substances

  • Argonaute Proteins
  • HLA Antigens
  • MicroRNAs
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases