Widespread 3'UTR capped RNAs derive from G-rich regions in proximity to AGO2 binding sites.
Year: 2024
Type: article
Abstract: The 3' untranslated region (3'UTR) plays a crucial role in determining mRNA stability, localisation, translation and degradation. Cap analysis of gene expression (CAGE), a method for the detection of capped 5' ends of mRNAs, additionally reveals a large number of apparently 5' capped RNAs derived from locations within the body of the transcript, including 3'UTRs. Here, we provide direct evidence that these 3'UTR-derived RNAs are indeed capped and widespread in mammalian cells. By using a combination of AGO2 enhanced individual nucleotide resolution UV crosslinking and immunoprecipitation (eiCLIP) and CAGE following siRNA treatment, we find that these 3'UTR-derived RNAs likely originate from AGO2-binding sites, and most often occur at locations with G-rich motifs bound by the RNA-binding protein UPF1. High-resolution imaging and long-read sequencing analysis validate several 3'UTR-derived RNAs, showcase their variable abundance and show that they may not co-localise with the parental mRNAs. Taken together, we provide new insights into the origin and prevalence of 3'UTR-derived RNAs, show the utility of CAGE-seq for their genome-wide detection and provide a rich dataset for exploring new biology of a poorly understood new class of RNAs.
Source: Figshare
Authors: Haberman, Nejc, Digby, Holly, Faraway, Rupert, Cheung, Rebecca, Chakrabarti, Anob M, Jobbins, Andrew M, Parr, Callum, Yasuzawa, Kayoko, Kasukawa, Takeya, Yip, Chi Wai, Kato, Masaki, Takahashi, Hazuki, Carninci, Piero, Vernia, Santiago, Ule, Jernej, Sibley, Christopher R, Martinez-Sanchez, Aida, Lenhard, Boris
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6964054817
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