# Molecular and genetic analysis of novel Slicer-dependent miRNA pathways in blood

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $732,071

## Abstract

PROJECT ABSTRACT
Molecular and genetic analysis of novel Slicer-dependent miRNA pathways in blood
 Most conserved microRNAs (miRNAs) are generated by a biogenesis pathway
that deposits them into an Argonaute effector, guiding them to broad regulatory target
networks. Amongst the cohort of four mammalian Argonautes, only Ago2 has catalytic
ability to cleave transcripts, an enzymatic activity known as "Slicing" that underlies
experimental RNA interference. Nevertheless, the endogenous biological usage of
mammalian Slicing remains largely mysterious. Our previous and ongoing studies
provide the unexpected perspective of multiple Slicing-dependent biogenesis strategies
that generate both Dicer-independent and Dicer-dependent erythroid miRNAs. These
data strongly support our hypothesis that a dominant usage of Ago2 catalysis is to
generate specific conserved miRNAs in the blood system. Our extensive preliminary
data are the basis of (1) a series of biochemical and genomic experiments to elucidate a
novel Slicing-dependent miRNA biogenesis mechanism, (2) genetic studies of novel
knockout animals of erythroid, Slicing-dependent miRNAs in normal development, blood
homeostasis and leukemia, and (3) molecular genetic analyses that seek to connect
dysregulated processes in Ago2-catalytically defective blood system to specific Slicing-
dependent miRNAs. These studies will bring new insights on post-transcriptional control
of erythroid development, homeostasis, and blood cancer, as well as pinpoint the
functional basis of mammalian RNAi to the generation of erythroid-specific miRNAs.

## Key facts

- **NIH application ID:** 9846225
- **Project number:** 5R01HL135564-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Michael Kharas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $732,071
- **Award type:** 5
- **Project period:** 2017-04-10 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846225

## Citation

> US National Institutes of Health, RePORTER application 9846225, Molecular and genetic analysis of novel Slicer-dependent miRNA pathways in blood (5R01HL135564-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846225. Licensed CC0.

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