RNA Therapeutics Institute; Program in Bioinformatics and Integrative Biology
Biochemistry, Biophysics, and Structural Biology | Cell and Developmental Biology | Genetics and Genomics | Therapeutics
Protein-coding genes undergo a wide array of regulatory interactions with factors that engage non-coding regions. Open reading frames (ORFs), in contrast, are thought to be constrained by coding function, precluding a major role in gene regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene silencing in C. elegans and show that marked differences in the sensitivity to piRNA silencing map to the endogenous sequences within transgene ORFs. Artificially increasing piRNA targeting within the ORF of a resistant transgene can lead to a partial yet stable reduction in expression, revealing that piRNAs not only silence but can also "tune" gene expression. Our findings support a model that involves a temporal element to mRNA regulation by germline Argonautes, likely prior to translation, and suggest that piRNAs afford incremental control of germline mRNA expression by targeting the body of the mRNA, including the coding region.
Argonautes, C. elegans, P granules, gene expression, nonsense-mediated decay, perinuclear germline nuage, piRNAs
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DOI of Published Version
Cell Rep. 2018 Feb 27;22(9):2254-2264. doi: 10.1016/j.celrep.2018.02.009. Epub 2018 Feb 15. Link to article on publisher's site
Seth M, Shirayama M, Tang W, Shen E, Tu S, Lee H, Weng Z, Mello CC. (2018). The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation in C. elegans. RNA Therapeutics Institute Publications. https://doi.org/10.1016/j.celrep.2018.02.009. Retrieved from https://escholarship.umassmed.edu/rti_pubs/4
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