Publications by authors named "Rohit Setlem"

Genome sequencing (GS) is a powerful clinical tool used for the comprehensive diagnosis of germline disorders. GS library preparation typically involves mechanical DNA fragmentation, end repair, and bead-based library size selection followed by adapter ligation, which can require a large amount of input genomic DNA. Tagmentation using bead-linked transposomes can simplify the library preparation process and reduce the DNA input requirement.

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Article Synopsis
  • Chemical modifications of RNAs play a crucial role in gene regulation, particularly through m^6A methylation mediated by the METTL3-METTL14 complex.
  • Mutations in METTL14, common in cancer, lead to altered m^6A modification patterns, promoting malignant cell growth without increasing overall m^6A levels in mRNAs.
  • The study proposes a structural model explaining how the METTL3-METTL14 complex selectively modifies specific RNA sequences, emphasizing the significance of noncanonical methylation in altering gene expression and contributing to cancer development.
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Unlabelled: Long noncoding RNAs have been implicated in many of the hallmarks of cancer. Herein, we found that the expression of lncRNA152 (lnc152; a.k.

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Article Synopsis
  • Cancer-associated mutations in histone genes result in the creation of oncohistones, which can affect cell growth in breast and ovarian cancer cells.
  • Six out of 25 screened mutant histones (H2B, H3, and H4) showed altered growth effects in various cell lines, with specific mutations inhibiting ADP-ribosylation.
  • The study demonstrates that mutations like H2B-D51 disrupt important post-translational modifications, contributing to tumor growth while not affecting PARP inhibition resistance, highlighting a potential mechanism for cancer cell survival.
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Miscarriage is a common complication of pregnancy for which there are few clinical interventions. Deficiency in endometrial stromal cell decidualization is considered a major contributing factor to pregnancy loss; however, our understanding of the underlying mechanisms of decidual deficiency are incomplete. ADP ribosylation by PARP-1 and PARP-2 has been linked to physiological processes essential to successful pregnancy outcomes.

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During gestation, the female reproductive tract must maintain pregnancy while concurrently preparing for parturition. Here, we explore the transitions in gene expression and protein turnover (fractional synthesis rates [FSR]) by which the cervix implements a transition from rigid to compliant. Shifts in gene transcription to achieve immune tolerance and alter epithelial cell programs begin in early pregnancy.

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Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, its role in physiological processes and gene expression has remained elusive. We found that NAD-dependent ADP-ribosylation of histone H2B-Glu35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of adjacent H2B-Ser36, which is required for the proadipogenic gene expression program. The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD synthase, which directs PARP-1 catalytic activity to Glu and Asp residues.

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