The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators

The heptad repeats of the C-terminal domain (CTD) of RNA polymerase II (Pol II) are extensively modified throughout the transcription cycle. The CTD coordinates RNA synthesis and processing by recruiting transcription regulators as well as RNA capping, splicing and 3'end processing factors. The SPOC domain of PHF3 was recently identified as a CTD reader domain specifically binding to phosphorylated serine-2 residues in adjacent CTD repeats. Here, we establish the SPOC domains of the human proteins DIDO, SHARP (also known as SPEN) and RBM15 as phosphoserine binding modules that can act as CTD readers but also recognize other phosphorylated binding partners. We report the crystal structure of SHARP SPOC in complex with CTD and identify the molecular determinants for its specific binding to phosphorylated serine-5. PHF3 and DIDO SPOC domains preferentially interact with the Pol II elongation complex, while RBM15 and SHARP SPOC domains engage with writers and readers of mA, the most abundant RNA modification. RBM15 positively regulates mA levels and mRNA stability in a SPOC-dependent manner, while SHARP SPOC is essential for its localization to inactive X-chromosomes. Our findings suggest that the SPOC domain is a major interface between the transcription machinery and regulators of transcription and co-transcriptional processes

PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay

The nature and impacts of fines in smelter-grade alumina

Fines in smelter-grade aluminas art recognized (is a significant process problem in aluminum smelting. However understanding the nature of this fine material and how it impacts the reduction process arc, less clearly understood The combination of new analytical methods such as variable pressure scanning electron microscopy and very; high field solid state nuclear magnetic resonance provide new insights into the phases present and their spatial distribution within aluminas, and suggest how such fine materials are generated, particularly during calcination in the alumina refinery

Imaginary companions and young children’s responses to ambiguous auditory stimuli: Implications for typical and atypical development

Background: Previous research has reported a link between imaginary companions (ICs) in middle childhood and the perception of verbal material in ambiguous auditory stimuli. These findings have been interpreted in terms of commonalities in the cognitive processes underlying children's engagement with ICs and adults’ reporting of imaginary verbal experiences such as auditory verbal hallucinations. The aim of the present study was to examine these relations using improved methodology and a younger sample of children for whom engagement with ICs would be expected to be particularly salient. Method: Data on young children's (age range: 4–8 years) reporting of ICs were gathered in two studies (total N = 80). Responses to ambiguous auditory stimuli were investigated using the new Jumbled Speech task, which measures participants’ likelihood of perceiving words in meaningless but speech-like auditory stimuli. Results: Reporting hearing words in the Jumbled Speech task was associated with having a parentally corroborated IC. Hearing words on the task and having an IC were unrelated to age, gender, verbal ability, and understanding of the stream of consciousness. Conclusions: Findings are consistent with the hypothesis that engaging with ICs is one aspect of a general susceptibility to imaginary verbal experiences. We consider the implications for the assumption of continuity in psychopathological experiences between childhood and adulthood