MYCN recruits the nuclear exosome complex to RNA polymerase II to prevent transcription-replication conflicts

MYC: a complex problem

“…Belying the seeming simplicity of iterative, processive nucleotide addition, the transcription-cycle progresses through sequential exchanges and interactions between multiple, multicomponent complexes [63]. Besides polymerase to add nucleotides in RNA synthesis, these stages involve and require multiple enzymatic activities including protein kinases, helicases, protein O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), poly-ADP-ribose polymerase (PARP), and nucleases as the RNA polymerase II (RNAPII)transcription machinery transits through initiation, promoter escape, early elongation, pausing and pause release, elongation, and termination [64][65][66][67][68][69][70]. Among the MYC-interacting transcription machinery complexes are TFIID, TFIIH, TFIIF, Mediator, PAF1, p-TEFb, and the exosome [15,30,56,71,72].…”

“…Several studies depict the role of both MYC and MYCN in the transcription cycle as variously modulating RNAPII binding to promoter, promoter escape, inducing pause release, and clearing impediments created by R loops and DNA damage [19,64,71,73]. MYC's many roles in transcription have been attributed to its recruitment of multiple partners.…”

“…MYC participates in CDC45 recruitment and CDK activity at origins and may help to regulate the spatiotemporal pattern of origin positioning and firing. Other studies suggest that MYC deregulation increased the chances of replication fork-transcription collision [50,64]. unstructured MYC empower efficient remodeling of energy landscape to drive the transcription cycle through a still incompletely enumerated set of transitions that regulate the magnitude and precision of promoter output in general or may be exploited at individual genes or gene sets.…”

Generation of a pooled shRNA library for functional genomics screens

“…This protocol will generate high-quality inducible libraries suitable for both genome-wide and targeted functional genomics screens, allowing the high-throughput interrogation of protein depletion effects in the cell system of choice. For complete details on the use and execution of this protocol, please refer to Papadopoulos et al. (2022) .…”

“…For complete details on the use and execution of this protocol, please refer to Papadopoulos et al. (2022) .…”