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Published on: May 1, 2021
CSDE1 promotes miR-451 biogenesis
Pavan Kumar Kakumani1, Yunkoo Ko2, Sushmitha Ramakrishna1
1Department of Biochemistry, Memorial University of Newfoundland, 45 Arctic Avenue, St. John's NL A1C 5S7, Canada.
Abstract:
MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and instead relies on AGO2 for its maturation. miR-451 is highly expressed in erythrocytes and regulates the differentiation of erythroblasts into mature red blood cells. However, the mechanistic details underlying miR-451 biogenesis in erythrocytes remains obscure. Here, we report that the RNA binding protein CSDE1 which is required for the development of erythroblasts into erythrocytes, controls the expression of miR-451 in erythroleukemia cells. CSDE1 binds miR-451 and regulates AGO2 processing of pre-miR-451 through its N-terminal domains. CSDE1 further interacts with PARN and promotes the trimming of intermediate miR-451 to the mature length. Together, our results demonstrate that CSDE1 promotes biogenesis of miR-451 in erythroid progenitors.
Insights
The RNA binding protein CSDE1 controls microRNA-451 (miR-451) biogenesis in red blood cell precursors. CSDE1 regulates AGO2 processing and PARN trimming, promoting mature miR-451 production in erythroid progenitors.
Area of Science:
- Molecular Biology
- Gene Regulation
- Hematopoiesis
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, typically processed by Drosha and Dicer.
- miR-451 is a conserved miRNA crucial for erythrocyte differentiation, bypassing Dicer for AGO2-mediated maturation.
- The precise mechanisms of miR-451 biogenesis in erythrocytes are not fully understood.
Purpose of the Study:
- To elucidate the role of RNA binding protein CSDE1 in miR-451 biogenesis.
- To investigate how CSDE1 influences the maturation of miR-451 in erythroid cells.
Main Methods:
- Analysis of CSDE1 binding to miR-451 precursors.
- Investigating CSDE1's interaction with AGO2 and PARN in erythroleukemia cells.
- Assessing the impact of CSDE1 on miR-451 processing and maturation.
Main Results:
- CSDE1 directly binds to pre-miR-451, regulating its processing by AGO2 via its N-terminal domains.
- CSDE1 interacts with PARN, facilitating the trimming of intermediate miR-451 to its mature form.
- CSDE1 expression is critical for miR-451 maturation in erythroid progenitor cells.
Conclusions:
- CSDE1 plays a vital role in promoting miR-451 biogenesis within erythroid progenitors.
- CSDE1 acts as a scaffold, coordinating AGO2 and PARN activities for efficient miR-451 maturation.
- These findings reveal a novel regulatory pathway for miRNA biogenesis in red blood cell development.
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