Researchers discovered that cells that are deficient in the survival motor neuron (SMN) protein exhibit increased ribosomal DNA damage and published their results in Life Science Alliance.

Spinal muscular atrophy (SMA) is a disease characterized by abnormally low levels of the SMN protein. The phenotype of this disease is progressive muscular atrophy and weakness which leads to early mortality. The genetic cause of this disease is the homozygous mutation or deletion of the SMN1 gene.

Karyka and colleagues reported that existing medical literature suggests that SMN-deficient cells exhibit ribosomal DNA damage. Ribosomal DNA transcription and assembly take place in the nucleolus. Hence, the nucleolus can be said to be the “ribosome factory” of a cell. Ribosomal DNA damage can disrupt the function and activity of the nucleolus.

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“The repetitive nature of [ribosomal DNA] coupled with its high transcription rates could lead to improper recombination and potential [ribosomal DNA] deletions or rearrangements as well as to the formation of RNA/DNA hybrid structures known as R-loops, composed of a displaced single-stranded DNA hybridized with the nascent transcript,” the authors of the study wrote.

Read more about SMA etiology 

Studies indicate that there is a higher incidence of R-loops in cells that are SMN-deficient. Clinical trials have demonstrated that changes occur in the nucleolar morphology of SMA type 1 fibroblasts. Scientists have suggested that disruptions in nucleolar architecture are caused by persistent ribosomal DNA damage. “Hence, we hypothesized that nucleolar abnormalities may be linked to alterations in [ribosomal DNA] integrity,” Karyka et al wrote.

The authors conducted their own study to test this hypothesis. Their data demonstrated an increase of R-loops in SMA cells compared to the control, reinforcing the idea that ribosomal DNA damage in SMA is mediated by R-loops.

“Taken together, these data support the idea that SMN deficiency leads to nucleolar disruption and increased R-loop–mediated [ribosomal DNA] damage,” they concluded.


Karyka E, Berrueta Ramirez N, Webster CP, et al. SMN-deficient cells exhibit increased ribosomal DNA damageLife Sci Alliance. 2022;5(8):e202101145. doi:10.26508/lsa.202101145