Publications by authors named "Hope E Merens"
Splicing is a highly regulated process critical for proper pre-mRNA maturation and the maintenance of a healthy cellular environment. Splicing events are impacted by ongoing transcription, neighboring splicing events, and cis and trans regulatory factors on the respective pre-mRNA transcript. Within this complex regulatory environment, splicing kinetics have the potential to influence splicing outcomes but have historically been challenging to study in vivo.
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- Mitochondrial oxidative phosphorylation (OXPHOS) complexes are made from proteins encoded by both nuclear and mitochondrial DNA, creating a challenge for coordinated gene expression across organelles.
- Researchers conducted genome-wide screens to discover genes essential for the synthesis of dual-origin protein complexes, leading to the identification of the uncharacterized genes PREPL and NME6.
- PREPL influences Complex IV biogenesis by linking lipid metabolism to protein synthesis, while NME6 plays multiple roles in OXPHOS biogenesis, including maintaining nucleotide levels and regulating mitoribosome assembly.
Article Synopsis
- The study focuses on RNA polymerase II (RNA Pol II) pausing, which is important for gene regulation but difficult to study due to the essential nature of pause-release factors.
- Researchers found mutations in the SUPT5H gene linked to β-thalassemia that disrupt RNA Pol II's pause release during the transition from progenitor to precursor cells in erythropoiesis (red blood cell formation).
- These mutations led to delayed differentiation and altered gene expression in erythroid cells, highlighting RNA Pol II pausing's role in coordinating cell cycle progression and differentiation in blood cell development.
Article Synopsis
- The study investigates the role of paused RNA polymerase II (Pol II) in gene regulation, particularly in the context of β-thalassemia and its effects on erythropoiesis (red blood cell formation).
- Researchers found mutations in the SPT5 gene that disrupt the proper release of paused Pol II, leading to delays in the transition from progenitor to precursor cells in healthy human cells.
- Despite these delays in gene expression and the cell cycle during differentiation, the cells eventually reach terminal differentiation, indicating that Pol II pausing plays a critical role in synchronizing the processes of proliferation and differentiation.
Article Synopsis
- Mitochondrial oxidative phosphorylation (OXPHOS) complexes are made from proteins coded by both nuclear and mitochondrial DNA, which complicates how cells regulate gene expression across these organelles.* ! -
- Researchers conducted genome-wide screening of mutant cells to discover genes that help balance levels of mitochondrial- and nuclear-encoded subunits in OXPHOS complexes, specifically cytochrome oxidase (Complex IV).* ! -
- They identified new genes involved in OXPHOS assembly, including PREPL and NME6, with NME6 playing a crucial role in supporting mitochondrial gene expression and ensuring proper mitochondrial function.* !
During maturation, eukaryotic precursor RNAs undergo processing events including intron splicing, 3'-end cleavage, and polyadenylation. Here we describe nanopore analysis of co-transcriptional processing (nano-COP), a method for probing the timing and patterns of RNA processing. An extension of native elongating transcript sequencing, which quantifies transcription genome-wide through short-read sequencing of nascent RNA 3' ends, nano-COP uses long-read nascent RNA sequencing to observe global patterns of RNA processing.
View Article and Find Full Text PDFThe aggregation and deposition of tau is a hallmark of a class of neurodegenerative diseases called tauopathies. Despite intensive study, cellular and molecular factors that trigger tau aggregation are not well understood. Here, we provide evidence for two mechanisms relevant to the initiation of tau aggregation in the presence of cytoplasmic polyphosphates (polyP): changes in the conformational ensemble of monomer tau and noncovalent cross-linking of multiple tau monomers.
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