PT  - JOURNAL ARTICLE
AU  - Evangelia Karyka
AU  - Nelly Berrueta Ramirez
AU  - Christopher P Webster
AU  - Paolo M Marchi
AU  - Emily J Graves
AU  - Vinay K Godena
AU  - Lara Marrone
AU  - Anushka Bhargava
AU  - Swagat Ray
AU  - Ke Ning
AU  - Hannah Crane
AU  - Guillaume M Hautbergue
AU  - Sherif F El-Khamisy
AU  - Mimoun Azzouz
TI  - SMN-deficient cells exhibit increased ribosomal DNA damage
AID  - 10.26508/lsa.202101145
DP  - 2022 Aug 01
TA  - Life Science Alliance
PG  - e202101145
VI  - 5
IP  - 8
4099  - https://www.life-science-alliance.org/content/5/8/e202101145.short
4100  - https://www.life-science-alliance.org/content/5/8/e202101145.full
SO  - Life Sci. Alliance2022 Aug 01; 5
AB  - 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.