| First Author | Karyka E | Year | 2022 |
| Journal | Life Sci Alliance | Volume | 5 |
| Issue | 8 | PubMed ID | 35440492 |
| Mgi Jnum | J:324245 | Mgi Id | MGI:7275729 |
| Doi | 10.26508/lsa.202101145 | Citation | Karyka E, et al. (2022) SMN-deficient cells exhibit increased ribosomal DNA damage. Life Sci Alliance 5(8):e202101145 |
| abstractText | Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels of survival motor neuron (SMN) protein. SMN is a multifunctional protein that is implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention is being paid to the role of SMN in the maintenance of DNA integrity. DNA damage and genome instability have been linked to a range of neurodegenerative diseases. The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. Instability in rDNA has been associated with cancer, premature ageing syndromes, and a number of neurodegenerative disorders. Here, we report that SMN-deficient cells exhibit increased rDNA damage leading to impaired ribosomal RNA synthesis and translation. We also unravel an interaction between SMN and RNA polymerase I. Moreover, we uncover an spinal muscular atrophy motor neuron-specific deficiency of DDX21 protein, which is required for resolving R-loops in the nucleolus. Taken together, our findings suggest a new role of SMN in rDNA integrity. |
