The yeast phosphofructokinase β-subunit has ATP-dependent RNA unwinding activity and modulates cell cycle progression

Phosphofructokinase (PFK) is a rate-limiting glycolytic enzyme that also possesses an unexplored RNA binding activity. Here, we show that the α- and β-subunits of yeast PFK, encoded by PFK1 and PFK2 , respectively, bind hundreds of mRNAs in cells, including one’s coding for proteins involved in regulation of mitotic cell cycle. Pkf2p directly binds in a Mg-ATP-dependent manner to short GA-, UC-, AU- and U-rich motifs overrepresented in its mRNA targets. Strikingly, Pfk2p displays directional 5’ - 3’ double-stranded RNA unwinding activity not seen with Pfk1p. Furthermore, Pfk2p dynamically associates with ribosomes and promotes translation of cell cycle genes. Consequently, pfk2Δ, but not pfk1Δ, mutant cells show severely delayed G1/S phase transition which is independent of the enzyme’s glycolytic activity. Our results uncovered a hidden function for the Pfk2 subunit as a translational activator of mitotic cell cycle gene transcripts possibly through energy-dependent RNA unwinding activity.