Back to Search
Start Over
Genome-wide analysis of pseudogenes reveals HBBP1’s human-specific essentiality in erythropoiesis and implication in β-thalassemia
- Source :
- Developmental Cell. 56:478-493.e11
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The human genome harbors 14,000 duplicated or retroposed pseudogenes. Given their functionality as regulatory RNAs and low conservation, we hypothesized that pseudogenes could shape human-specific phenotypes. To test this, we performed co-expression analyses and found that pseudogene exhibited tissue-specific expression, especially in the bone marrow. By incorporating genetic data, we identified a bone-marrow-specific duplicated pseudogene, HBBP1 (η-globin), which has been implicated in β-thalassemia. Extensive functional assays demonstrated that HBBP1 is essential for erythropoiesis by binding the RNA-binding protein (RBP), HNRNPA1, to upregulate TAL1, a key regulator of erythropoiesis. The HBBP1/TAL1 interaction contributes to a milder symptom in β-thalassemia patients. Comparative studies further indicated that the HBBP1/TAL1 interaction is human-specific. Genome-wide analyses showed that duplicated pseudogenes are often bound by RBPs and less commonly bound by microRNAs compared with retropseudogenes. Taken together, we not only demonstrate that pseudogenes can drive human evolution but also provide insights on their functional landscapes.
- Subjects :
- Heterogeneous Nuclear Ribonucleoprotein A1
RNA Stability
Pseudogene
Regulator
Biology
Binding, Competitive
General Biochemistry, Genetics and Molecular Biology
Cell Line
03 medical and health sciences
0302 clinical medicine
Erythroid Cells
Species Specificity
Bone Marrow
microRNA
Gene duplication
Humans
Erythropoiesis
RNA, Messenger
Molecular Biology
T-Cell Acute Lymphocytic Leukemia Protein 1
030304 developmental biology
Genetics
0303 health sciences
Protein Stability
beta-Thalassemia
Cell Differentiation
Cell Biology
Phenotype
Globins
Organ Specificity
RNA, Long Noncoding
Human genome
Pseudogenes
030217 neurology & neurosurgery
Protein Binding
Developmental Biology
TAL1
Subjects
Details
- ISSN :
- 15345807
- Volume :
- 56
- Database :
- OpenAIRE
- Journal :
- Developmental Cell
- Accession number :
- edsair.doi.dedup.....24fc41788369e3de17a94cab4d9c651c