Understanding microRNA targeting with high-throughput biochemistry

MicroRNAs (miRNAs) are short RNAs that, in complex with Argonaute (AGO) proteins, guide repression of mRNA targets. miRNAs negatively regulate most mammalian mRNAs, and disruption of this regulation often results in severe defects at the cellular and organismal level. miRNA repression occurs primarily through base-pairing between the miRNA seed region (nucleotides 2-8) and mRNA 3'-UTR sites, leading to transient recruitment of mRNA-destabilizing factors. However, only a small fraction of the gene-expression changes caused by a miRNA can currently be predicted, which precludes a deeper understanding of how miRNA regulation impacts the animal transcriptome. miRNA targeting efficacy should in principle be a function of the affinity between AGO-miRNA complexes and their targets. However, only a few such measurements had been reported, with measured values differing from those predicted for RNA-RNA pairing in solution.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2021

Author dc:creator

• McGeary, Sean E.(Sean Edward)

Advisor dc:contributor.advisor

• David P. Bartel.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/130661

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/130661