New article published in Nucleic Acid Research

02/02/2021

Non-perfectly matching small RNAs can induce stable and heritable epigenetic modifications and can be used as molecular markers to trace the origin and fate of silencing RNAs 

Yue Fei, Tünde Nyikó, Attila Molnar

Link: academic.oup.com/nar/advance-article/doi/10.1093/nar/gkab023/6125661?login=true

Short (21–24 nucleotide long) non-coding RNAs (sRNAs) play a fundamental role in gene regulation and development in higher organisms. sRNAs act as molecular postcodes and guide specific proteins for targeted mRNA degradation/destabilization and DNA methylation. Despite their importance, very little is known about the target selection rules that govern sRNA-induced DNA methylation. To test whether mutations in the sRNAs, referred to as mismatches, can alter their function, we chose a transgene (Green Fluorescent Protein, GFP) and an endogene (FWA) as a reporter system. We delivered the mismatched sRNAs via recombinant viruses and monitored their activity by phenotypic and molecular assays. We found that mismatched sRNAs are capable of inducing DNA methylation, which resulted in GFP and FWA silencing. The former is manifested as red leaf due to the autofluorescence of chlorophyll in the lack of GFP expression (top panel) and the latter is associated with early flowering (bottom panel).

Our novel sRNA tracking method allowed us to monitor the origin, activity and fate of sRNAs for the first time. Our finding demonstrates unexpected flexibility in sRNA-induced transgenerational DNA methylation and opens new avenues to investigate the intimate interaction between invading molecules such as transposons and viruses and the epigenome.