Biology subjects

Conic, S.

Publications and source records attributed to Conic, S..

3 recordsLinked to original sources

bioRxiv2025

RNA polymerase II initiation factors show different dynamic behaviour upon induced transcription in live cells

Transcription by RNA polymerase II (Pol II) requires the ordered action of general transcription factors (GTFs) forming the pre-initiation complex (PIC). How these events unfold kinetically remains unclear. Upon transcription activation, we observe coordinated recruitment of Pol II and GTFs together with chromatin decompaction. Pol II and its Ser5-phosphorylated form accumulate and persist at promoters, whereas TFIIB and TFIIF engage transiently, revealing distinct dynamic regimes. We find specific residence kinetics consistent with rapid exchange of GTFs and a more stable initiating Pol II population. A quantitative kinetic model recapitulates the temporal ordering and relative amplitudes of factor recruitment, predicts recruitment times, and links transient GTF engagement to sustained Pol II occupancy. Steady state measurements and transcription inhibition corroborate model predictions. These results uncover a dynamic hierarchy in human PIC assembly and establish a quantitative framework that connects factor exchange kinetics to the regulation of Pol II activity in living cells.

molecular biology↗

bioRxiv2018

Co-translation drives the assembly of mammalian nuclear multisubunit complexes

AO_SCPLOWBSTRACTC_SCPLOWCells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding proteins assembling in the same multisubunit complexes are dispersed in the genome of eukaryotes, it is unclear how multisubunit complexes assemble. We show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits but lacking precise architectural details are built co-translationally. We demonstrate that the dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). Our results indicate that protein translation and complex assembly are linked in building mammalian multisubunit complexes and suggest that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will significantly advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.

molecular biology↗

bioRxiv2018

A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation

Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.

developmental biology↗