Small nucleolar RNAs (snoRNAs) are noncoding RNAs primarily known for guiding chemical modifications of RNA, but their broader cellular roles and contributions to human diseases remain elusive. This In Focus article introduces the development of snoRNA-enriched kethoxal-assisted RNA-RNA sequencing (snoKARR-seq), a transcriptome-wide approach to uncover snoRNA targets with enhanced sensitivity and specificity. This method revealed an unexpected role for snoRNAs in protein translocation and secretion, expanding our understanding of their noncanonical functions.
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