PT  - JOURNAL ARTICLE
AU  - Balendra, Rubika
AU  - Ruiz de los Mozos, Igor
AU  - Odeh, Hana M
AU  - Glaria, Idoia
AU  - Milioto, Carmelo
AU  - Wilson, Katherine M
AU  - Ule, Agnieszka M
AU  - Hallegger, Martina
AU  - Masino, Laura
AU  - Martin, Stephen
AU  - Patani, Rickie
AU  - Shorter, James
AU  - Ule, Jernej
AU  - Isaacs, Adrian M
TI  - Transcriptome-wide RNA binding analysis of C9orf72 poly(PR) dipeptides
AID  - 10.26508/lsa.202201824
DP  - 2023 Sep 01
TA  - Life Science Alliance
PG  - e202201824
VI  - 6
IP  - 9
4099  - http://www.life-science-alliance.org/content/6/9/e202201824.short
4100  - http://www.life-science-alliance.org/content/6/9/e202201824.full
SO  - Life Sci. Alliance2023 Sep 01; 6
AB  - An intronic GGGGCC repeat expansion in C9orf72 is a common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The repeats are transcribed in both sense and antisense directions to generate distinct dipeptide repeat proteins, of which poly(GA), poly(GR), and poly(PR) have been implicated in contributing to neurodegeneration. Poly(PR) binding to RNA may contribute to toxicity, but analysis of poly(PR)-RNA binding on a transcriptome-wide scale has not yet been carried out. We therefore performed crosslinking and immunoprecipitation (CLIP) analysis in human cells to identify the RNA binding sites of poly(PR). We found that poly(PR) binds to nearly 600 RNAs, with the sequence GAAGA enriched at the binding sites. In vitro experiments showed that poly(GAAGA) RNA binds poly(PR) with higher affinity than control RNA and induces the phase separation of poly(PR) into condensates. These data indicate that poly(PR) preferentially binds to poly(GAAGA)-containing RNAs, which may have physiological consequences.