TY - JOUR TI - One-shot analysis of translated mammalian lncRNAs with AHARIBO AU - Minati, Luca AU - Firrito, Claudia AU - Del Piano, Alessia AU - Peretti, Alberto AU - Sidoli, Simone AU - Peroni, Daniele AU - Belli, Romina AU - Gandolfi, Francesco AU - Romanel, Alessandro AU - Bernabo, Paola AU - Zasso, Jacopo AU - Quattrone, Alessandro AU - Guella, Graziano AU - Lauria, Fabio AU - Viero, Gabriella AU - Clamer, Massimiliano A2 - Chang, Howard Y A2 - Manley, James L A2 - Rinn, John L VL - 10 PY - 2021 DA - 2021/02/17 SP - e59303 C1 - eLife 2021;10:e59303 DO - 10.7554/eLife.59303 UR - https://doi.org/10.7554/eLife.59303 AB - A vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode peptides, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated and peptide-producing lncRNAs. Here, we present AHA-mediated RIBOsome isolation (AHARIBO), a method for the detection of lncRNAs either untranslated, but associated with ribosomes, or encoding small peptides. Using AHARIBO in mouse embryonic stem cells during neuronal differentiation, we isolated ribosome-protected RNA fragments, translated RNAs, and corresponding de novo synthesized peptides. Besides identifying mRNAs under active translation and associated ribosomes, we found and distinguished lncRNAs acting as ribosome sponges or encoding micropeptides, laying the ground for a better functional understanding of hundreds of lncRNAs. KW - LncRNA KW - proteogenomics KW - proteomics KW - translation KW - ribosome KW - RIBO-seq JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -