A higher order PUF complex is central to regulation of C. elegans germline stem cells

Qiu, C.; Crittenden, S. L.; Carrick, B.; Dillard, L.; Costa dos Santos, S.; Dandey, V.; Dutcher, R.; Viverette, E.; Wine, R.; Woodworth, J.; Campbell, Z.; Wickens, M.; Borgnia, M. J.; Kimble, J.; Hall, T.

doi:10.1101/2024.06.14.599074

bioRxiv · 10.1101/2024.06.14.599074

A higher order PUF complex is central to regulation of C. elegans germline stem cells

Qiu, C.·Crittenden, S. L.·Carrick, B.·Dillard, L.·Costa dos Santos, S.·Dandey, V.·Dutcher, R.·Viverette, E.·Wine, R.·Woodworth, J.·Campbell, Z.·Wickens, M.·Borgnia, M. J.·Kimble, J.·Hall, T.

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Abstract

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF-2 binding elements (FBEs) in its 3UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established canonical FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1-FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.

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Qiu, C., Crittenden, S. L., Carrick, B., Dillard, L., Costa dos Santos, S., Dandey, V., Dutcher, R., Viverette, E., Wine, R., Woodworth, J., Campbell, Z., Wickens, M., Borgnia, M. J., Kimble, J., Hall, T.. 2024-06-14. A higher order PUF complex is central to regulation of C. elegans germline stem cells. https://doi.org/10.1101/2024.06.14.599074

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