Human FASTK protein binds G-rich ssRNA

Human FASTK preferentially binds single-stranded and G-rich RNA.

Dawidziak DM, Dzadz DA, Kuska MI, Kanavalli M, Klimecka MM, Merski M, Bandyra KJ, Górna MW.

FEBS Journal (2025), DOI: 10.1111/febs.70155

Although FASTK is known to play a role in mRNA biology, the mechanism through which it recognizes RNA has yet to be unraveled. We used purified human FASTK to characterize its RNA-binding properties in vitro. We found that FASTK prefers ssRNA oligonucleotides containing guanines with the potential to form G-quadruplexes, and binds robustly to any longer RNA such as mitochondrial mRNA. Moreover, the addition of FASTK alone could protect RNA from degradation by the degradosome. Structural characterization using SAXS data and predicted models verified by mutagenesis experiments identified an RNA-binding interface in the central region of FASTK

This work was supported by the National Science Centre, Poland [grant agreement 2014/15/D/NZ1/00968 to MWG, 2020/37/N/NZ1/02348 to DMD, 2020/37/K/NZ1/02312 to KJB] and EMBO Installation Grant [3315]. The research leading to these results has received funding from the Norwegian Financial Mechanism 2014-2021 2020/37/K/NZ1/02312.