# Selective regulatory and biogenesis mechanisms for microRNAs

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $568,701

## Abstract

PROJECT ABSTRACT
 microRNAs (miRNAs) are an abundant class of small regulatory RNAs that
typically derive from stepwise cleavages of hairpin transcripts by the Drosha and Dicer
RNase III enzymes. The resulting mature miRNAs mediate extensive networks of post-
transcriptional regulation, and are implicated in a variety of diseases including cancer.
 This proposal extends our long-standing commitment to understanding atypical
strategies for microRNA biogenesis, and their implications during normal and
dysfunctional settings. For example, our past efforts uncovered diverse non-canonical
substrates that bypass Drosha and/or Dicer to yield active microRNAs. In current efforts,
we report unexpected insights into selective processing by Drosha and Dicer. First, we
gain insights from a non-canonical miRNA to propose a new general model for nuclear
microRNA biogenesis by Drosha and its cofactor DGCR8 at operons, which involves
novel cofactors. Second, we build on the observation that catalytic inactivation of Dicer is
selected in cancer to uncover selective biogenesis effects and unexpected molecular
and phenotypic consequences.
 We will dissect the models of underlying biogenesis mechanisms, and evaluate
the broader impacts of these regulatory strategies using genomic strategies. Overall, by
better understanding how microRNAs are generated, we will improve our capacity to
harness them experimentally, as well as help interpret recurrent diseases linked to
mutation of core microRNA biogenesis factors.

## Key facts

- **NIH application ID:** 10234809
- **Project number:** 2R01GM083300-14A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Eric C Lai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,701
- **Award type:** 2
- **Project period:** 2007-09-21 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234809

## Citation

> US National Institutes of Health, RePORTER application 10234809, Selective regulatory and biogenesis mechanisms for microRNAs (2R01GM083300-14A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10234809. Licensed CC0.

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