Publications by authors named "Jonathan Merran"

Background: Pharmacogenomics has demonstrated benefits for clinical care, including a reduction in adverse events and cost savings. However, barriers in expanded implementation of pharmacogenomics testing include prolonged turnaround times and integration of results into the electronic health record with clinical decision support. A clinical workflow was developed and implemented to facilitate in-house result generation and incorporation into the electronic health record at a large academic medical center.

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RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442.

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Termination of RNA polymerase II (Pol II) transcripts occurs through two alternative pathways. Termination of mRNAs is coupled to cleavage and polyadenylation while noncoding transcripts are terminated through the Nrd1-Nab3-Sen1 (NNS) pathway in a process that is linked to RNA degradation by the nuclear exosome. Some mRNA transcripts are also attenuated through premature termination directed by the NNS complex.

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Article Synopsis
  • The study investigates RNA splicing fidelity and highlights the role of various proteins, including TDP-43, PTBP1, and PTBP2, in repressing nonconserved cryptic exons.
  • While TDP-43 uses UG microsatellites for repression, PTBP1 and PTBP2 use CU microsatellites to target both conserved tissue-specific and nonconserved cryptic exons.
  • The findings suggest that PTBP1 and PTBP2 are part of a larger family of splicing factors that help regulate transcript diversity necessary for neuronal differentiation.
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Article Synopsis
  • Yeast RNA polymerase II (Pol II) terminates coding transcripts via the polyadenylation (pA) pathway and non-coding transcripts through the non-polyadenylation (non-pA) pathway.
  • PAR-CLIP was used to analyze Pol II positioning in living yeast after depleting components of these termination complexes.
  • Key findings include that Ysh1 is crucial for efficient Pol II removal at pA sites, while depletion of Nrd1 or Sen1 affects termination of non-pA transcripts differently, with Nrd1 causing extensive runaway elongation and Sen1 leading to less effective readthrough.
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