Widespread 3′UTR capped RNAs derive from G-rich regions in proximity to AGO2 binding sites

Autor: Nejc Haberman, Holly Digby, Rupert Faraway, Rebecca Cheung, Anob M. Chakrabarti, Andrew M. Jobbins, Callum Parr, Kayoko Yasuzawa, Takeya Kasukawa, Chi Wai Yip, Masaki Kato, Hazuki Takahashi, Piero Carninci, Santiago Vernia, Jernej Ule, Christopher R. Sibley, Aida Martinez-Sanchez, Boris Lenhard
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Biology, Vol 22, Iss 1, Pp 1-23 (2024)
Druh dokumentu: article
ISSN: 1741-7007
DOI: 10.1186/s12915-024-02032-7
Popis: 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. Graphical Abstract Schematic representation of the proposed model where 3′UTR-derived RNAs originate from G-rich regions enriched in AGO2 and UPF1 binding sites.
Databáze: Directory of Open Access Journals
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