Nuclear-localized tiny RNAs are associated with transcription initiation and splice sites in metazoans. Homo sapiens

We have recently shown that transcription initiation RNAs (tiRNAs) are derived from sequences downstream of transcription start sites. Here we report the identification of a second class of nuclear-specific ~17-18 nucleotide small RNA whose 3’ ends map precisely to the splice donor site of internal exons in animals. These splice-site RNAs (spliRNAs) are associated with highly expressed genes, and show evidence of developmental stage- and region-specific expression. We also confirm that tiRNAs are nuclear localized, enriched at chromatin marks associated with transcription initiation, and possess a 3’ nucleotide bias. Additionally, we find that microRNA-offset RNAs (moRNAs), the oncogenic miR-15/16 cluster and most snoRNA-derived small RNAs (sdRNAs) are enriched in the nucleus, whereas most miRNAs and two H/ACA sdRNAs are cytoplasmically enriched. We propose that nuclear localized tiny RNAs are involved in epigenetic regulation of gene expression. Overall design: Discovery and characterization of small RNA species through high-througput deep sequencing of nuclear, cytoplasmic and total small RNA fractions from THP-1 cells, a monocytic leukemia cell line. Additional files and information are available at http://matticklab.com/index.php?title=NuclearTinyRNAs