Human box C/D snoRNA processing conservation across multiple cell types

Small nucleolar RNAs (snoRNAs) function mainly as guides for the post-transcriptional modification of ribosomal RNAs (rRNAs). In recent years, several studies have identified a wealth of small fragments (<35nt) derived from snoRNAs (termed sdRNAs) that stably accumulate in the cell, some of which may regulate splicing or translation. A comparison of human small RNA deep sequencing data sets reveals that box C/D sdRNA accumulation patterns are conserved across multiple cell types although the ratio of the abundance of different sdRNAs from a given snoRNA varies. sdRNA profiles of many snoRNAs are specific and resemble the cleavage profiles of miRNAs. Many do not show characteristics of general RNA deg-radation, as seen for the accumulation of small fragments derived from snRNA or rRNA. While 53 % of the sdRNAs contain an snoRNA box C motif and boxes D and D0 are also common in sdRNAs (54%), relatively few (12%) contain a full snoRNA guide region. One box C/D snoRNA, HBII-180C, was analysed in greater detail, revealing the presence of C0 box-containing sdRNAs com-plementary to several pre-messenger RNAs (pre-mRNAs) including FGFR3. Functional analyses demonstrated that this region of HBII-180C can influence the alternative splicing of FGFR3 pre-mRNA, supporting a role for some snoRNAs in the regulation of splicing