Grant: Project Grant

Small RNAs form several large families of biomolecules emerging as essential regulators of fundamental cellular processes. While miRNAs, a large family of cytoplasmic small RNAs regulating transcript stability on widespread levels, have been extensively characterized, nuclear small RNAs are also emerging as fundamental regulators performing varied roles. The conserved family of small nucleolar RNAs (snoRNAs) are a group of such nuclear small RNAs. SnoRNAs have been well-characterized as guiding the chemical modification of ribosomal RNAs, an important step in ribosome biogenesis and ultimately in protein synthesis. However, over the past 5 years, many independent reports have identified specific snoRNAs as involved in diverse other functions ranging from the maturation of pre-messenger RNAs to the response to stress in the cytoplasm. By analysis of deep-sequencing datasets of small RNAs of several human cell lines, we identified groups of snoRNAs differing in terms of their protein binding preferences and terminal sequences, suggesting they could play different regulatory roles in the cell. In light of these recent findings, we propose to characterise specific families and subgroups of small RNAs and to define their role in the regulation of essential nuclear processes, using computational and experimental methods. Many small RNAs display significantly deregulated expression in cancer and a subset have been shown to play an important role in cancer development and maintenance. This study will shed light on a large group of nuclear regulators of gene expression that have been generally ignored in this role, significantly increasing our understanding of the multi-layered regulation of gene expression.