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Measurements of the turbulent density wavenumber spectrum, δne(k⊥), using the Doppler Back-Scattering (DBS) diagnostic are reported from DIII-D H-mode plasmas with electron cyclotron heating (ECH) as the only auxiliary heating method. These electron-heated plasmas have low collisionality, ν*e < 1, Te/Ti > 1, and zero injected torque – a regime expected to be relevant for future fusion devices. We probe density fluctuations in the core (ρ ≈ 0.7) over a broad wavenumber range, 0.5 ≤ k⊥ ≤ 16 cm–1 (0.1 ≤ k⊥ρs ≤ 5) to characterize plasma instabilities and compare with theoretical predictions. We present a novel synthetic DBS diagnostic to relate the back-scattered power spectrum, Ps(k⊥) – which is directly measured by DBS – to the underlying electron density fluctuation spectrum, δne(k⊥). The synthetic DBS Ps(k⊥) spectrum is calculated by combining the SCOTTY beam-tracing code with a model δne(k⊥) predicted either analytically or numerically. In this work we use the quasi-linear code TGLF to approximate the δne(k⊥) spectrum. We find that TGLF, using the experimental profiles, is capable of closely reproducing the DBS measurements. Both the DBS measurements and the TGLF-DBS synthetic diagnostic show a wavenumber spectrum with variable decay. The measurements show weak decay (k–0.6) for k < 3.5 cm–1, with k–2.6 at intermediate-k (3.5 ≤ k ≤ 8.5 cm–1), and rapid decay (k–9.4) for k > 8.5 cm–1. Scans of physics parameters using TGLF suggest that the normalized ∇Te scale-length, R/LTe, is an important factor for distinguishing microturbulence regimes in these plasmas. A combination of DBS observations and TGLF simulations indicate that fluctuations remain peaked at ITG-scales (low k) while R/LTe-driven TEM/ETG-type modes (intermediate/high k) are marginally sub-dominant.

Reduced oxygen availability (hypoxia) triggers adaptive cellular responses via hypoxia-inducible factor (HIF)-dependent transcriptional activation. Adaptation to hypoxia also involves transcription-independent processes like post-translational modifications; however, these mechanisms are poorly characterized. Investigating the involvement of protein SUMOylation in response to hypoxia, we discovered that hypoxia strongly decreases the SUMOylation of Exosome subunit 10 (EXOSC10), the catalytic subunit of the RNA exosome, in an HIF-independent manner. EXOSC10 is a multifunctional exoribonuclease enriched in the nucleolus that mediates the processing and degradation of various RNA species. We demonstrate that the ubiquitin-specific protease 36 (USP36) SUMOylates EXOSC10 and we reveal SUMO1/sentrin-specific peptidase 3 (SENP3) as the enzyme-mediating deSUMOylation of EXOSC10. Under hypoxia, EXOSC10 dissociates from USP36 and translocates from the nucleolus to the nucleoplasm concomitant with its deSUMOylation. Loss of EXOSC10 SUMOylation does not detectably affect rRNA maturation but affects the mRNA transcriptome by modulating the expression levels of hypoxia-related genes. Our data suggest that dynamic modulation of EXOSC10 SUMOylation and localization under hypoxia regulates the RNA degradation machinery to facilitate cellular adaptation to low oxygen conditions.

The internal stem loop (ISL) of the human U6 snRNA, which catalyzes pre-mRNA splicing, contains LARP7-dependent, snoRNA-guided 2′- O -methylations and an N 2 -methylguanosine (m 2 G) that is required for splicing of weak splice sites. Here, we show that installation of m 2 G 72 by the THUMPD2-TRMT112 methyltransferase complex is one of the last maturation events during U6 snRNP biogenesis. We dissect features of THUMPD2 required for association with U6 and present an experimentally validated model of the THUMPD2-TRMT112-U6 complex. Using in vitro methylation assays as well as a newly developed m 2 G-sensitive deoxyribozyme to monitor U6-m 2 G 72 levels in cellular RNAs, we reveal that 2′- O -methylations within the U6 ISL enhance methylation of G 72 . We show that m 2 G 72 and the 2′- O -methylations in U6 independently and interdependently influence alternative splicing. Furthermore, our data demonstrate that 2′- O -methylations in the ISL are required for incorporation of U6 into snRNPs whereas m 2 G 72 influences the progression of the U6 snRNP into larger assemblies, highlighting distinct roles of these modifications during spliceosome assembly. The U6 snRNA internal stem loop (ISL) forms the catalytic core of the spliceosome. Here, the authors reveal a hierarchal modification pathway for the U6 ISL, and highlight the independent and interdependent importance of modified nucleotides in the ISL for snRNP maturation and optimal pre-mRNA splicing.

The internal stem loop (ISL) of the human U6 snRNA, which catalyzes pre-mRNA splicing, contains LARP7-dependent, snoRNA-guided 2'-O-methylations and an N -methylguanosine (m G) that is required for splicing of weak splice sites. Here, we show that installation of m G by the THUMPD2-TRMT112 methyltransferase complex is one of the last maturation events during U6 snRNP biogenesis. We dissect features of THUMPD2 required for association with U6 and present an experimentally validated model of the THUMPD2-TRMT112-U6 complex. Using in vitro methylation assays as well as a newly developed m G-sensitive deoxyribozyme to monitor U6-m G levels in cellular RNAs, we reveal that 2'-O-methylations within the U6 ISL enhance methylation of G . We show that m G and the 2'-O-methylations in U6 independently and interdependently influence alternative splicing. Furthermore, our data demonstrate that 2'-O-methylations in the ISL are required for incorporation of U6 into snRNPs whereas m G influences the progression of the U6 snRNP into larger assemblies, highlighting distinct roles of these modifications during spliceosome assembly.

Reduced oxygen availability (hypoxia) triggers adaptive cellular responses via hypoxia-inducible factor (HIF)-dependent transcriptional activation. Adaptation to hypoxia also involves transcription-independent processes like post-translational modifications, however these mechanisms are poorly characterized. Investigating the involvement of protein SUMOylation in response to hypoxia, we discovered that hypoxia strongly decreases the SUMOylation of Exosome subunit 10 (EXOSC10), the catalytic subunit of the RNA exosome, in a HIF-independent manner. EXOSC10 is a multifunctional exoribonuclease enriched in the nucleolus that mediates the processing and degradation of various RNA species. We demonstrate that the Ubiquitin-specific protease 36 (USP36) SUMOylates EXOSC10 and we reveal SUMO1/sentrin-specific peptidase 3 (SENP3) as the enzyme mediating deSUMOylation of EXOSC10. Under hypoxia, EXOSC10 dissociates from USP36 and translocates from the nucleolus to the nucleoplasm concomitant with its deSUMOylation. Loss of EXOSC10 SUMOylation does not detectably affect rRNA maturation but affects the mRNA transcriptome by modulating the expression levels of hypoxia-related genes. Our data suggest that dynamic modulation of EXOSC10 SUMOylation and localization under hypoxia regulates the RNA degradation machinery to facilitate cellular adaptation to low oxygen conditions.