Basak et al. 2019 (PRJNA545050)

General Details

Title Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation (Ribo-seq, RNA-seq)
Organism
Number of Samples 16
Release Date 2019/05/28 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP199612
ENA SRP199612
GEO
BioProject PRJNA545050

Publication

Title
Authors Basak A,Munschauer M,Lareau CA,Montbleau KE,Ulirsch JC,Hartigan CR,Schenone M,Lian J,Wang Y,Huang Y,Wu X,Gehrke L,Rice CM,An X,Christou HA,Mohandas N,Carr SA,Chen JJ,Orkin SH,Lander ES,Sankaran VG
Journal Nature genetics
Publication Date 2020 Feb
Abstract Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia 1 . BCL11A represses the genes encoding HbF and regulates human hemoglobin switching through variation in its expression during development 2-7 . However, the mechanisms underlying the developmental expression of BCL11A remain mysterious. Here we show that BCL11A is regulated at the level of messenger RNA (mRNA) translation during human hematopoietic development. Despite decreased BCL11A protein synthesis earlier in development, BCL11A mRNA continues to be associated with ribosomes. Through unbiased genomic and proteomic analyses, we demonstrate that the RNA-binding protein LIN28B, which is developmentally expressed in a pattern reciprocal to that of BCL11A, directly interacts with ribosomes and BCL11A mRNA. Furthermore, we show that BCL11A mRNA translation is suppressed by LIN28B through direct interactions, independently of its role in regulating let-7 microRNAs, and that BCL11A is the major target of LIN28B-mediated HbF induction. Our results reveal a previously unappreciated mechanism underlying human hemoglobin switching that illuminates new therapeutic opportunities.
PMC PMC7031047
PMID 31959994
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR9132358 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132359 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132360 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132361 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132362 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132363 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132364 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132365 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132366 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132367 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132368 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132369 PRJNA545050 Homo sapiens hematopoetic cells_adult erythroid cells Ribo-Seq Cycloheximide
SRR9132370 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132371 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132372 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
SRR9132373 PRJNA545050 Homo sapiens hematopoetic cells_newborn erythroid cells Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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