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

## TL;DR

A subunit of a glycolytic enzyme in yeast can unwind RNA and influence cell cycle progression, linking energy metabolism to cell proliferation.

## Contribution

Discovery of RNA unwinding activity in the Pfk2 subunit of yeast phosphofructokinase and its role in cell cycle regulation.

## Key findings

- Pfk2p unwinds RNA in a 5′–3′ direction and binds specific RNA motifs in cell cycle-related mRNAs.
- Pfk2p promotes translation of cell cycle genes and associates with ribosomes.
- Loss of Pfk2p causes increased cell size and delayed G1/S phase transition independent of glycolytic activity.

## Abstract

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 functionally related messenger RNAs (mRNAs) in cells, including one’s coding for proteins involved in the regulation of mitotic cell cycle. Both Pfk1p and Pkf2p directly bind to short GA-, UC-, AU-, and U-rich motifs overrepresented in their 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, pfk2∆, but not pfk1∆, mutants display increased cell sizes and severely delayed G1/S phase transition, 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, thus providing a link between central energy metabolism and cell proliferation.

Graphical Abstract