Longevity & AgingCellular RNA cleanup crew protects blood stem cells from DNA damage and lymphoma risk
Blood stem cells must keep transcribing genes while protecting their DNA. Transcription produces many unneeded RNA molecules, and these can form R loops, structures where RNA stays bound to DNA and can cause breaks. This study examined the nuclear exosome targeting (NEXT) complex, which sends unneeded nascent RNAs to the RNA exosome for degradation. When the authors deleted ZCCHC8, a core NEXT subunit, in the blood-forming system of mice, hematopoietic stem cells lost self-renewal capacity. The cells accumulated R loops, showed more DNA lesions, and activated DNA repair pathways. The authors also report that ZCCHC8 is frequently dysregulated in diffuse large B cell lymphoma (DLBCL) and that this is linked to poorer clinical outcomes. They propose NEXT as a protector of stem cell genome integrity and a possible therapeutic target in DLBCL. These findings are preclinical and based on the abstract alone.
