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Our new paper is out! Special thanks to @PabloManavella and @PlantEvolution, and all the co-author for their contribution! @AxelGiudicatti, @AgustinLArce, Delfina_Gagliardi, @Lei_Li0601, Wei_Yuan and @DerekSeveri https://www.cell.com/molecular-plant/fulltext/S1674-2052(20)30450-0#.X-yUbdxenqo.twitter
After 20 years suggesting that HASTY (HST) export miRNAs from nuclei, we demonstrate that HST is far from acting as a miRNA cargo protein, instead it modulates miRNA biogenesis linking transcription and processing
HST shuttling between nuclei and cytoplasm depends on its interaction with RAN1 (to be translocated from the nucleus) and IMPA-2 (to be translocated to the nucleus). But mutations of either HST, RAN1 and IMPA-2 do not affect the subcellular distribution of miRNAs
Then, HST function is uncoupled to miRNA translocation between nuclei and cytoplasm. Mutation in HST downregulates several miRNAs, and accumulates their mRNA targets and pri-miRNAs. Which is the function of HST on miRNA pathway?
HST neither affect DCL1 activity in vitro nor interacts with pri-miRNAs. Then, HST activity may not directly modulate miRNA processing.
HST directly interacts by its N-terminal domain with DCL1, and by its C-terminal portion with the MEDITOR subunits MED37- D and -E and MED20. DCL1 and MED37 do not directly interact, but the presence of HST induce or stabilize a complex between the three proteins.
We found that both MED37 and HST are associated to MIR genes. Moreover,DCL1 is recruited to nascent pri-miRNA in an HST-dependent manner. Then, MED complex may recruit HST, and HST stabilizes a complex together with DCL1 during pri-miRNA transcription, leading to miRNA biogenesis
How HST is recruited to the MIR genes? Does HST function as a cargo transporter? Which cargos may it transport? Lots of new questions around HST…
