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Kos-Braun, I. C.

Publications and source records attributed to Kos-Braun, I. C..

2 recordsLinked to original sources
bioRxiv2019

Two molecules of Has1 RNA helicase function simultaneously in the biogenesis of small and large ribosomal subunits

The RNA helicase Has1 is involved in the biogenesis of both small and large ribosomal subunits. How it performs these separate roles is not fully understood. Here we provide evidence that two molecules of Has1 are recruited and temporarily present in the same time in 90S pre-ribosomes. We identified multiple Has1 binding sites in the 18S, 5.8S and 25S rRNAs. We show that while the Has1 catalytic activity is not required for binding to 5.8S/25S region in pre-rRNA, it is essential for binding to 18S sites. After the cleavage of pre-rRNA at the site A2 Has1 remains associated not only with pre-60S but unexpectedly also with the pre-40S ribosomes. The recruitment to 90S/pre-40S and pre-60S ribosomes is mutually independent. Our data reconcile some seemingly contradictory observations about Has1 function in ribosome biogenesis.

molecular biology↗
bioRxiv2019

A ribosome assembly stress response regulates transcription to maintain proteome homeostasis

Ribosome biogenesis is a complex and energy-demanding process requiring tight coordination of ribosomal RNA (rRNA) and ribosomal protein (RP) production. Alteration of any step in this process may impact growth by leading to proteotoxic stress. Although the transcription factor Hsf1 has emerged as a central regulator of proteostasis, how its activity is coordinated with ribosome biogenesis is unknown. Here we show that arrest of ribosome biogenesis in the budding yeast S. cerevisiae triggers rapid activation of a highly specific stress pathway that coordinately up-regulates Hsf1 target genes and down-regulates RP genes. Activation of Hsf1 target genes requires neo-synthesis of RPs, which accumulate in an insoluble fraction, leading to sequestration of the RP transcriptional activator Ifh1. Our data suggest that levels of newly-synthetized RPs, imported into the nucleus but not yet assembled into ribosomes, work to continuously balance Hsf1 and Ifh1 activity, thus guarding against proteotoxic stress during ribosome assembly.

molecular biology↗