Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect.

Takahashi et al. 1 Takahashi T. Stoiljkovic M. Song E. Gao X.-B. Yasumoto Y. Kudo E. Carvalho F. Kong Y. Park A. Shanabrough M. et al. LINE-1 activation in the cerebellum drives ataxia. Neuron. 2022; 110: 3278-3287.e8 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar recently concluded that the retrotransposon LINE-1 (L1) drives neurodegeneration in ataxia telangiectasia (AT). They reported increased cerebellar L1 RNA abundance in AT patients, as measured by RNA sequencing (RNA-seq), as well as ataxia and neurodegeneration in mice where cerebellar L1 transcription was increased by a CRISPR-dCas9 approach. This study could shape future strategies to treat or prevent AT in children, and, for this reason, its findings warrant careful consideration. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effectTakahashi et al.NeuronMarch 01, 2023In BriefIn his letter, Dr. Faulkner argues that L1HS is not significantly increased in ataxia telangiectasia (AT) patients’ cerebella. It notes that there are increased intronic reads in AT, which correlate with L1 reads; thus, increased L1 reads are the reflection of higher intronic reads. The letter contends that artifactual factors such as RNA qualities might be the cause of reported differences, and our findings with human samples should be omitted from the paper. We thank Dr. Faulkner for his interest in our study, and we have performed additional experiments to address these issues. Full-Text PDF LINE-1 activation in the cerebellum drives ataxiaTakahashi et al.NeuronSeptember 6, 2022In BriefTakahashi et al. found elevated expression of the transposable element LINE-1 in the cerebella of ataxia telangiectasia patients. A mouse model in which LINE-1 is activated in cerebellar Purkinje neurons showed significant ataxia with neurodegeneration and electrophysical abnormalities. The progression of the ataxia was attenuated with a reverse transcriptase inhibitor treatment. Full-Text PDF Open Access