12.8.19, Variants of RNA exporters repurposed to fulfil new functions

Two new papers from the Brennecke Lab (IMBA), published last week in Cell and in Nature Structural & Molecular Biology, describe “adaptive radiation” of RNA export proteins.

The Brennecke Lab studies a small RNA-based genome immune system that suppresses transposon activity in animals. Now two novel aspects of the system have been discovered by the team.

The 22-30 nt piRNAs, which guide transposon silencing, are processed in the cytoplasm from longer non-coding RNAs. However, these precursor transcripts lack RNA quality hallmarks that render transcripts export-competent, thus the question: how do they bypass these export control checkpoints? Now Mostafa ElMaghraby, Peter R. Andersen et al. revealed a unique travelling route for these regulatory RNAs:

A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production
ElMaghraby MF, Andersen PR, Pühringer F, Hohmann U, Meixner K, Lendl T, Tirian L, Brennecke J.
Cell. 2019 Aug 8;178(4):964-979.e20. doi: 10.1016/j.cell.2019.07.007.

Congrats for the great work, especially to Mostafa, DK RNA Biology student member and shared first author of the work!

Further downstream in the piRNA-mediated pathway, it was only poorly understood how the piRNA-guided targeting of Piwi proteins to nascent transposon transcripts leads to co-transcriptional silencing of transposons on molecular level. Now Julia Batki, Jakob Schnabl et al. have identified the SFiNX complex containing, among other factors, a variant of the RNA export factor which seems to have evolved a new function, playing a central role in heterochromatin formation at transposon loci:

The nascent RNA binding complex SFiNX licenses piRNA-guided heterochromatin formation
Batki J, Schnabl J, Wang J, Handler D, Andreev VI, Stieger CE, Novatchkova M, Lampersberger L, Kauneckaite K, Xie W, Mechtler K, Patel DJ, Brennecke J.
Nat Struct Mol Biol. 2019 Aug;26(8):720-731. doi: 10.1038/s41594-019-0270-6. Epub 2019 Aug 5

Congrats to the whole lab, especially Julia and Jakob, both DK RNA Biology members/alumnis and shared first authors of this work!