RT Journal Article
SR Electronic
T1 SMN-deficient cells exhibit increased ribosomal DNA damage
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101145
DO 10.26508/lsa.202101145
VO 5
IS 8
A1 Evangelia Karyka
A1 Nelly Berrueta Ramirez
A1 Christopher P Webster
A1 Paolo M Marchi
A1 Emily J Graves
A1 Vinay K Godena
A1 Lara Marrone
A1 Anushka Bhargava
A1 Swagat Ray
A1 Ke Ning
A1 Hannah Crane
A1 Guillaume M Hautbergue
A1 Sherif F El-Khamisy
A1 Mimoun Azzouz
YR 2022
UL https://www.life-science-alliance.org/content/5/8/e202101145.abstract
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.