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Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation.

Abstract：

:Erythropoiesis is regulated at multiple levels to ensure the proper generation of mature red cells under multiple physiological conditions. To probe the contribution of long noncoding RNAs (lncRNAs) to this process, we examined >1 billion RNA-seq reads of polyadenylated and nonpolyadenylated RNA from differentiating mouse fetal liver red blood cells and identified 655 lncRNA genes including not only intergenic, antisense, and intronic but also pseudogene and enhancer loci. More than 100 of these genes are previously unrecognized and highly erythroid specific. By integrating genome-wide surveys of chromatin states, transcription factor occupancy, and tissue expression patterns, we identify multiple lncRNAs that are dynamically expressed during erythropoiesis, show epigenetic regulation, and are targeted by key erythroid transcription factors GATA1, TAL1, or KLF1. We focus on 12 such candidates and find that they are nuclear-localized and exhibit complex developmental expression patterns. Depleting them severely impaired erythrocyte maturation, inhibiting cell size reduction and subsequent enucleation. One of them, alncRNA-EC7, is transcribed from an enhancer and is specifically needed for activation of the neighboring gene encoding BAND 3. Our study provides an annotated catalog of erythroid lncRNAs, readily available through an online resource, and shows that diverse types of lncRNAs participate in the regulatory circuitry underlying erythropoiesis.

journal_name

Blood

journal_title

Blood

authors

Alvarez-Dominguez JR,Hu W,Yuan B,Shi J,Park SS,Gromatzky AA,van Oudenaarden A,Lodish HF

doi

10.1182/blood-2013-10-530683

subject

Has Abstract

pub_date

2014-01-23 00:00:00

pages

570-81

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2013-10-530683

journal_volume

123

pub_type

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