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IMPLICATING RIBONUCLEASES IN MAMALIAN TAILED MIRTRON BIOGENESIS
Author(s) -
Zia Farid,
Flynt Alex
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04664
Subject(s) - drosha , dicer , biology , genetics , microrna , rna splicing , alternative splicing , intron , gene , ribonuclease iii , rna binding protein , untranslated region , rna , computational biology , messenger rna , rna interference
MicroRNAs are pervasive small noncoding ~22 nt gene regulators that collectively control gene expression by destabilizing mRNA through repressing translation. Since they are broadly involved in cell differentiation and maintenance, they are linked to most diseases including the major causes of mortality, heart disease and cancer. Several thousand miRNA genes have been reported in mammals that typically generated thorough a canonical pathway involving sequential cleavage by Drosha and Dicer, however, there are many non‐canonical miRNAs that mature through alternative pathways. Mirtrons are the most abundant class of atypical miRNA that bypass Drosha cleavage step and instead are produced by splicing. Following lariat debranching, the host intron RNA can be exported to cytoplasm for Dicer processing. There are 3 classes of mirtrons: conventional, 5′‐tailed, and 3′‐tailed. In tailed mirtrons, splicing defines only pre‐miRNA hairpin end. While a mechanism has been reported for 3′‐tailed mirtrons, processing of 5′‐tailed varieties remains a mystery. Here, we studied the biogenesis of human and mouse 5′‐tailed mirtrons to implicate RNases in tail processing. Through a mutational approach we have identified endocnucleolytic cleavage of precursors to be important to processing of 5′‐tailed mirtrons. This is a novel mechanism that contrasts with what has been shown for 3′ tailed mirtrons. Our findings shed light on the most substantial variety of mirtrons encoded by the human genome. Support or Funding Information This work was supported by the National Institute of Health and also Mississippi INBRE program (R15GM120716‐01).