Thread by @thatdnaguy

#ASHG20 HYC
Genome Regulation by Long Noncoding RNAs.
Howard Y. Chang.

#ASHG20 HYC RNA localizatin is both a prevalent phenomenon and an important one. Variation that affects RNA localization can lead to phenotypic differences.

#ASHG20 HYC If you understand where RNA is going you can understand more about what it does.

#ASHG20 HYC APEX-Seq - a proximity RNA labeling and sequencing method. Fuse APEX protein to a landmark protein in the cell. Labels RNA in close physical proximity 5 - 10 nm resolution.

#ASHG20 HYC HEK293 cells tested with 9 different landmarks labeling different components of the cell (nucleus, cytoplasm, mitochondrial membrane, mito matrix, etc).

#ASHG20 HYC Example - XIST. You see that it is in the nucleus and in close proximity to lamin B1. Different transcripts show different patterns. IARS2. Mature forms only seen in outer mitochondrial membrane.

#ASHG20 HYC >3000 human RNAs show specific sub-cellular localization. Some transcript localize to nucleus, many are long non-coding RNAs. Most transcripts are localized to just 1 or 2 locations, but not diffusely all over the cell.

#ASHG20 HYC Introns are retained in some transcripts through various defects. Where does this go? Most retained introns are excluded from the nuclear pore. Get stuck in nuclear lamina.

#ASHG20 HYC Isoform switching can cause changes in RNA localization.

#ASHG20 HYC Make RNA-GPS - a machine learning model of RNA localization.
Paper: bit.ly/3jJ6PTw
Area under curve 0.77. Precision / Recall 0.49.

#ASHG20 HYC Can mutagenize to see effect of localization. Can also apply RNA-GPS for RNA sub-cellular localization of viruses. Example of SARS-CoV2. Predicts several RNA localization signals.

#ASHG20 HYC Double membrane vesicles are important for SARS-CoV-2 replication. Where does membrane come from? Suggest maybe mitochondria as it has a double-membrane normally.