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Bazzini Lab

We seek to understand how genes are regulated at the post-transcriptional level during vertebrate development and in human disease, and to uncover the mechanisms underlying the translation and stability of messenger RNA.

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Research Summary

What dictates the stability of mRNA?

Research Areas

Molecular and Cell Biology, Development and Regeneration, Genetics and Genomics

Organisms

Zebrafish, Human cell lines

The Bazzini Lab investigates how gene regulation impacts development, physiology, and disease. The lab’s primary focus is to determine the regulatory factors governing mRNA stability and its translation into protein. Traditionally, transcription - the production of mRNA gene messages from DNA - has been thought to be the major determinant of mRNA quantity and quality; however, mRNA stability may be equally important.

The assumption that mRNAs in higher organisms contain a single protein-coding region, or open reading frame (ORF), has undergone a dramatic revision in recent years. The lab has identified thousands of small translated ORFs within previously assigned untranslated regions (UTRs), and long non-coding RNAs. Analyzing ribosomal profiling data from human cell lines and zebrafish embryos has enabled the discovery of small translated ORFs in the 3’UTRs, referred to as downstream ORFs (dORFs).

Principal Investigator

Ariel Bazzini

Associate Investigator

Stowers Institute for Medical Research

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Science

Codon optimality can determine mRNA stability and transcription. Codons, the three-nucleotide ‘words’ of mRNA read by protein-producing ribosomes, have a strong effect on the stability of maternal mRNA supplied to the embryo, and thus contain information that extends far beyond the protein sequences they encode. This represents a paradigm shift in how mRNA stability is viewed.

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Our Team

Featured Publications

iCodon customizes gene expression based on the codon composition

Diez M, Medina-Munoz SG, Castellano LA, da Silva Pescador G, Wu Q, Bazzini AA. Sci Rep. 2022;12:12126 doi: 10.1038/s41598-022-15526-7.

Optimized CRISPR-RfxCas13d system for RNA targeting in zebrafish embryos

Hernandez-Huertas L, Kushawah G, Diaz-Moscoso A, Tomas-Gallardo L, Moreno-Sanchez I, da Silva Prescador G, Bazzini AA, Moreno-Mateos MA. STAR-Protocol. 2022;3:101058.  doi: 10.1016/j.xpro.2021.101058..

Crosstalk between codon optimality and cis-regulatory elements dictates mRNA stability

Medina-Munoz SG, Kushawah G, Castellano LA, Diez M, DeVore ML, Salazar MJB, Bazzini AA. [published ahead of print January 7 2021]. Genome Biol. 2021;22:14. doi: 10.1186/s13059-020-02251-5.

Translation of small downstream ORFs enhances translation of canonical main open reading frames

Wu Q, Wright M, Gogol MM, Bradford WD, Zhang N, Bazzini AA. EMBO J. 2020;39:e104763. doi: 104710../embj.2020104763.

CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos

Kushawah G, Hernandez-Huertas L, Abugattas-Nunez Del Prado J, Martinez-Morales JR, DeVore ML, Hassan H, Moreno-Sanchez I, Tomas-Gallardo L, Diaz-Moscoso A, Monges DE, Guelfo JR, Theune WC, Brannan EO, Wang W, Corbin TJ, Moran AM, Sanchez Alvarado A, Malaga-Trillo E, Takacs CM, Bazzini AA, Moreno-Mateos MA.  Dev Cell. 2020;54:805-817 e807.

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