Impaired glycoRNA biogenesis in metabolic-dysfunction associated steatotic liver disease.

GlycoRNA biogenesis is significantly impaired in human MASLD livers, with most glycoRNAs reduced by approximately 50%, contributing to disease progression.

• Why it matters: Understanding molecular mechanisms underlying MASLD is critical due to its high prevalence and limited treatment options, highlighting the need for novel biomarkers and therapeutic targets.
• What they did: The study identified glycoRNAs in human liver tissues and cells, and demonstrated that decreased expression of biosynthesis mediators SIDT1 and DTWD2 contributes to glycoRNA loss; restoration via AAV vectors improved disease markers in mice.
• The result: Restoring glycoRNA biosynthesis attenuated fatty liver injury in preclinical models, suggesting glycoRNAs as potential biomarkers and therapeutic targets for MASLD, with implications for early diagnosis and intervention.