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Updated: Jul 24, 2025
08:40
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
17.7K
Target-directed microRNA degradation regulates developmental microRNA expression and embryonic growth in mammals
Benjamin T Jones1, Jaeil Han1, He Zhang2
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Biorxiv : the Preprint Server for Biology
|July 10, 2023
Summary
Target-directed miRNA degradation (TDMD) controls microRNA (miRNA) levels. Loss of Zswim8, a key TDMD factor, caused developmental defects and revealed widespread miRNA regulation impacting mammalian body size.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- MicroRNAs (miRNAs) are crucial gene regulators in development and disease.
- Target-directed miRNA degradation (TDMD) is a pathway for controlling miRNA levels.
- The role and extent of TDMD regulation in mammals are not well understood.
Approach:
- Generated mice with constitutive or conditional deletion of Zswim8, an essential TDMD factor.
- Utilized small RNA sequencing on embryonic tissues to analyze miRNA regulation.
- Investigated the impact of TDMD on miRNA clusters and arm switching.
Key Points:
- Zswim8 deletion led to developmental defects, growth restriction, and perinatal lethality.
- Small RNA sequencing revealed extensive miRNA regulation by TDMD, expanding the known miRNA catalog.
- TDMD-regulated miRNAs are enriched in co-transcribed clusters and influence miRNA arm switching.
Conclusions:
- TDMD is a widespread regulatory mechanism in mammals with significant developmental roles.
- The TDMD pathway, through specific miRNAs like miR-322 and miR-503, directly influences mammalian body size.
- This study elucidates the broad landscape and developmental significance of TDMD in mammals.
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