Research reveals nucleolar RNA interference based on C. elegans as a model organism

A research group led by Professor GUANG Shouhong of the China University of Science and Technology (USTC) of the Chinese Academy of Sciences, together with Professor FENG Xuezhu of the USTC First Affiliate Hospital, revealed the ‘nucleolar RNA interference based on Caenorhabditis elegans (C. elegans) as a model organism. The study was published in Nuclear Acid Research.

SiRNA is a kind of small, non-coding RNA about 22 nucleotides in length. SiRNA plays an important role in growth and development, reproductive genetics and immune defense in animal and plant bodies, and is an excellent drug molecule.

Using direct and reverse genetic screening, Prof. GUANG’s group identified a series of siRNA suppressor factors (SUSI) that inhibit the endogenous production of siRNA in C. elegans. When the SUSI factor is defective, poorly processed ribosomal RNA (rRNA) fragments accumulate in cells, inducing the production of ribosomal siRNA (risiRNA). RisiRNAs complement rRNA sequences and regulate the level of rRNA by activating the nuclear RNA interference pathway.

In this study, researchers cloned a SUSI-5 gene that inhibits the production of risiRNA by genetic screening and found that the SUSI-5 gene encodes a conserved catalytic DIS-3 subunit of RNA exosomes.

Using CRISPR gene editing technology, they confirmed that the functional defect of any subunit of the RNA exosome could cause the accumulation of risiRNA, and that risiRNA induces two key interfering factors of nuclear RNA, NRDE-2 and NRDE-3, to enter the nucleolus, bind ribosomal RNA precursors, and then inhibit the transcriptional activity of RNA polymerase.

In addition, the researchers found that RNA exosomes could respond to rRNA homeostasis in the nucleus by altering subcellular localization. RNA exosomes play an important role in the processing and metabolism of a variety of RNAs and are primarily located in the nucleolus. The imbalance in the homeostasis of intracellular rRNAs would lead to the transfer of RNA exosomes from the nucleolus to the nucleoplasm. The correct subcellular localization of RNA exosomes plays an important role in inhibiting the production of risiRNA.

This study established a new model of rRNA surveillance that helps people understand the biological roles and mechanisms of risiRNAs.