Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development.
Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 polyadenylated lncRNAs expressed in erythroblasts, megakaryocytes, and megakaryocyte-erythroid precursors of mice, and 594 in erythroblasts of humans. More than half of these lncRNAs were unannotated, emphasizing the opportunity for new discovery through studies of specialized cell types. Analysis of the mouse erythro-megakaryocytic polyadenylated lncRNA transcriptome indicates that ~75% arise from promoters and 25% from enhancers, many of which are regulated by key transcription factors including GATA1 and TAL1. Erythroid lncRNA expression is largely conserved among 8 different mouse strains, yet only 15% of mouse lncRNAs are expressed in humans and vice versa, reflecting dramatic species-specificity. RNA interference assays of 21 abundant erythroid-specific murine lncRNAs in primary mouse erythroid precursors identified 7 whose knockdown inhibited terminal erythroid maturation. At least 6 of these 7 functional lncRNAs have no detectable expression in human erythroblasts, suggesting that lack of conservation between mammalian species does not predict lack of function.
Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
Vikram R
VR
Paralkar
Tejaswini
T
Mishra
Jing
J
Luan
Yu
Y
Yao
Andrew V
AV
Kossenkov
Stacie M
SM
Anderson
Margaret
M
Dunagin
Maxim
M
Pimkin
Meghneel
M
Gore
Diana
D
Sun
Neeraja
N
Konuthula
Arjun
A
Raj
Xiuli
X
An
Narla
N
Mohandas
David M
DM
Bodine
Ross C
RC
Hardison
Mitchell J
MJ
Weiss
D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D004900:Erythroblasts / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D006801:Humans; D055015:Megakaryocyte-Erythroid Progenitor Cells / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity; D034061:Thrombopoiesis / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
D062085:RNA, Long Noncoding; D014157:Transcription Factors