Molecular and genetic analysis of novel Slicer-dependent miRNA pathways in blood
Description: PROJECT NARRATIVE microRNAs (miRNAs) are ~22 nucleotide RNA molecules that guide Argonaute (Ago) effector complexes to target transcripts for repression. Collectively, miRNAs mediate broad gene regulatory networks with substantial impact on disease and cancer. Special Ago proteins, such as mammalian Ago2, have the ability to cleave target transcripts. This enzymatic activity, referred to as "Slicing", underlies the powerful experimental tecnique of RNA interference, but the endogenous biological significance of Slicing is poorly understood. Our previous and ongoing studies demonstrate that in mammals, Slicing activity is intimately and fundamentally tied to the erythroid system. In particular, we show that there are multiple non-canonical biogenesis mechanisms for erythroid-restricted miRNAs that uniquely require Ago2-Slicing activity. We propose a combination of biochemical, molecular, genetic, and genomewide studies to elucidate the biological requirements of non-canonical erythroid miRNAs, and how they surprisingly underlie the blood defects of Slicing-defective mammals.
Funding type: research
Funder scheme: R01
Start date: 2017-04-10
End date: 2022-01-31
Investigator: MICHAEL KHARAS
Institution: SLOAN-KETTERING INST CAN RESEARCH
Subfield: Cancer Research
Domain: Life Sciences
Funded outputs count: 33
Funder award ID: R01HL135564
OpenAlex ID: G2954331833