A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes.

Published online

Journal Article

BACKGROUND: Human erythrocytes are terminally differentiated, anucleate cells long thought to lack RNAs. However, previous studies have shown the persistence of many small-sized RNAs in erythrocytes. To comprehensively define the erythrocyte transcriptome, we used high-throughput sequencing to identify both short (18-24 nt) and long (>200 nt) RNAs in mature erythrocytes. RESULTS: Analysis of the short RNA transcriptome with miRDeep identified 287 known and 72 putative novel microRNAs. Unexpectedly, we also uncover an extensive repertoire of long erythrocyte RNAs that encode many proteins critical for erythrocyte differentiation and function. Additionally, the erythrocyte long RNA transcriptome is significantly enriched in the erythroid progenitor transcriptome. Joint analysis of both short and long RNAs identified several loci with co-expression of both microRNAs and long RNAs spanning microRNA precursor regions. Within the miR-144/451 locus previously implicated in erythroid development, we observed unique co-expression of several primate-specific noncoding RNAs, including a lncRNA, and miR-4732-5p/-3p. We show that miR-4732-3p targets both SMAD2 and SMAD4, two critical components of the TGF-β pathway implicated in erythropoiesis. Furthermore, miR-4732-3p represses SMAD2/4-dependent TGF-β signaling, thereby promoting cell proliferation during erythroid differentiation. CONCLUSIONS: Our study presents the most extensive profiling of erythrocyte RNAs to date, and describes primate-specific interactions between the key modulator miR-4732-3p and TGF-β signaling during human erythropoiesis.

Full Text

Duke Authors

Cited Authors

  • Doss, JF; Corcoran, DL; Jima, DD; Telen, MJ; Dave, SS; Chi, J-T

Published Date

  • November 16, 2015

Published In

Volume / Issue

  • 16 /

Start / End Page

  • 952 -

PubMed ID

  • 26573221

Pubmed Central ID

  • 26573221

Electronic International Standard Serial Number (EISSN)

  • 1471-2164

Digital Object Identifier (DOI)

  • 10.1186/s12864-015-2156-2

Language

  • eng

Conference Location

  • England