Henning Urlaub

Jun 20, 2024 | nature.com | Katarina Harasimov |Luisa M. Welp |Sarah Mae Penir |Yehor Horokhovskyi |Shiya Cheng |Katsuyoshi Takaoka | +13 more

Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman’s reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity. Mouse ovaries had more extremely long-lived proteins than other tissues, including brain. These long-lived proteins had diverse functions, including in mitochondria, the cytoskeleton, chromatin and proteostasis. The stable proteins resided not only in oocytes but also in long-lived ovarian somatic cells. Our data suggest that mammals increase protein longevity and enhance proteostasis by chaperones and cellular antioxidants to maintain the female germline for long periods. Indeed, protein aggregation in oocytes did not increase with age and proteasome activity did not decay. However, increasing protein longevity cannot fully block female germline senescence. Large-scale proteome profiling of ~8,890 proteins revealed a decline in many long-lived proteins of the proteostasis network in the aging ovary, accompanied by massive proteome remodeling, which eventually leads to female fertility decline. Harasimov, Gorry, Welp, Penir, Horokhovskyi et al. analyse proteostasis in mammalian oocytes and ovaries: the maintenance of oocytes involves exceptional protein longevity, and many of the extremely long-lived proteins decline as the ovary ages.

May 22, 2024 | nature.com | Zhenwei Zhang |VINAY KUMAR |Olexandr Dybkov |Henning Urlaub |Holger Stark

AbstractEarly spliceosome assembly can occur through an intron-defined pathway, whereby U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) assemble across the intron1. Alternatively, it can occur through an exon-defined pathway2,3,4,5, whereby U2 binds the branch site located upstream of the defined exon and U1 snRNP interacts with the 5′ splice site located directly downstream of it.

Apr 3, 2024 | nature.com | Isaac Fianu |Moritz Ochmann |James Walshe |Olexandr Dybkov |Henning Urlaub

AbstractThe Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript1, but has not explained how Integrator removes Pol II from the DNA template.

Nov 6, 2023 | nature.com | Ying Chen |Olexandr Dybkov |Henning Urlaub

AbstractElongin is a heterotrimeric elongation factor for RNA polymerase (Pol) II transcription that is conserved among metazoa. Here, we report three cryo-EM structures of human Elongin bound to transcribing Pol II. The structures show that Elongin subunit ELOA binds the RPB2 side of Pol II and anchors the ELOB–ELOC subunit heterodimer.

Sep 4, 2023 | nature.com | Thomas Berger |Henning Urlaub

AbstractThe reaction of CO2 with H2O to form bicarbonate (HCO3−) and H+ controls sperm motility and fertilization via HCO3−-stimulated cAMP synthesis. A complex network of signaling proteins participates in this reaction. Here, we identify key players that regulate intracellular pH (pHi) and HCO3− in human sperm by quantitative mass spectrometry (MS) and kinetic patch-clamp fluorometry. The resting pHi is set by amiloride-sensitive Na+/H+ exchange.