Human 28s rRNA 5’ terminal derived small RNA inhibits ribosomal protein mRNA levels

Recent small RNA (sRNA) high-throughput sequencing studies reveal ribosomal RNAs (rRNAs) as major resources of sRNA. By reanalyzing sRNA sequencing datasets from Gene Expression Omnibus (GEO), we identify 28s rRNA 5’ terminal derived sRNA (named 28s5-rtsRNA) as the most abundant rRNA-derived sRNAs. These 28s5-rtsRNAs show a length dynamics with identical 5’ end and different 3’ end. Through exploring sRNA sequencing datasets of different human tissues, 28s5-rtsRNA is found to be highly expressed in bladder, macrophage and skin. We also show 28s5-rtsRNA is independent of microRNA biogenesis pathway and not associated with Argonaut proteins. Overexpression of 28s5-rtsRNA could alter the 28s/18s rRNA ratio and decrease multiple ribosomal protein mRNA levels. Our results reveal that 28s5-rtsRNA serves as a key regulator in ribosomal protein expression.