Characterizing circular and linear non-coding RNA in human aged brains and their association with dementia

Le résumé fourni par la source

Total RNA, depleted of ribosomal RNA, is commonly used for RNA sequencing to capture both polyadenylated and non-polyadenylated transcripts, whereas poly(A) tail-targeting protocols can either enrich (Poly(A)-selection) or deplete (Poly(A)-depletion) the polyadenylated fraction. To ascertain the best library strategy for capturing long non-coding RNAs (lncRNAs, > 200nt) and circular RNAs (circRNAs) in aged brains, we applied three protocols (total ribo-depleted, poly(A)-selected, and poly(A)-depleted) to 128 human hippocampus samples. Our results show that both ribo-depleted and poly(A)-depleted perform well for lncRNA and circRNA profiling, with the poly(A)-depleted protocol generally detecting a slightly higher number of non-coding RNAs. Additionally, we compared poly(A)-selected and -depleted data for predicting the poly(A) status of hippocampal transcripts. The proportion of non-polyadenylated transcripts was higher than previously found. This study demonstrates how the choice of library construction affects outcomes, helping to make informed methodological choices when studying brain non-coding RNAs. In addition, we examined, for the first time, whether the poly(A) status of protein-coding mRNAs is associated with AD and AD-related dementias.

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