Molecular Biology

Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase

1. Hudson W Coates
2. Isabelle M Capell-Hattam
3. Ellen M Olzomer
4. Ximing Du
5. Rhonda Farrell
6. Hongyuan Yang
7. Frances L Byrne
8. Andrew J Brown

• Curated by eLife

  eLife assessment

  Hudson and colleagues provide a new link between oxygen sensing and cholesterol synthesis. In previous studies, this group had shown that the cholesterol synthetic enzyme squalene monooxygenase (SM) is subjected to partial proteasomal degradation, which leads to the production of a truncated, constitutively active enzyme. Here, the authors provide evidence for the physiological significance of SM truncation by showing that subjecting cells to hypoxia (oxygen deprivation) induces truncation of SM. The synthesis of cholesterol requires 11 molecules of oxygen and SM is the first oxygen-dependent enzyme in the cholesterol-committed branch of the pathway. It is possible that constitutive activation of SM under oxygen-deficient conditions could reduce the toxicity of squalene and other sterol intermediates.

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The role of Limch1 alternative splicing in skeletal muscle function

1. Matthew S. Penna
2. George G. Rodney
3. Rong-Chi Hu
4. Thomas A. Cooper

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Translational buffering by ribosome stalling in upstream open reading frames

1. Ty A. Bottorff
2. Heungwon Park
3. Adam P. Geballe
4. Arvind Rasi Subramaniam

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Drosophila cap-binding protein eiF4EHP promotes translation via a 3’UTR-dependent mechanism under hypoxia and contributes to fruit fly adaptation to oxygen variations

1. Manfei Liang
2. Clara Hody
3. Vanessa Yammine
4. Romuald Soin
5. Yuqiu Sun
6. Xing Lin
7. Xiaoying Tian
8. Romane Meurs
9. Camille Perdrau
10. Nadège Delacourt
11. Fabienne Andris
12. Louise Conrard
13. Véronique Kruys
14. Cyril Gueydan

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Nucleotide-level linkage of transcriptional elongation and polyadenylation

1. Joseph V Geisberg
2. Zarmik Moqtaderi
3. Nova Fong
4. Benjamin Erickson
5. David L Bentley
6. Kevin Struhl

• Curated by eLife

  eLife assessment

  Giesberg and colleagues provide evidence both in yeast and human cells that fast elongation speeds of RNA polymerases result in a "downstream-shifted" poly(A) profile while the opposite is true for slower speeds of elongating polymerases. GC content of sequences downstream of poly(A) clusters influences the cluster profiles by affecting elongation and thus allowing more time for the 3'-cleavage complex to find the poly(A) site and form the transcript terminus. Although the findings presented in this manuscript are not surprising, they are new and contribute a missing piece to our knowledge of how the transcription machinery determines which poly(A) site to utilize at the end of genes.

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Deep learning-driven insights into super protein complexes for outer membrane protein biogenesis in bacteria

1. Mu Gao
2. Davi Nakajima An
3. Jeffrey Skolnick

• Curated by eLife

  eLife assessment

  In this valuable contribution, the authors apply an artificial intelligence method to predict the three-dimensional structure of complexes of outer membrane proteins of the Gram-negative bacterium E. coli. Some of the cases presented are compelling, as they explain previously published biochemical data and/or reproduce existing structural data.

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m6A modification of U6 snRNA modulates usage of two major classes of pre-mRNA 5’ splice site

1. Matthew T Parker
2. Beth K Soanes
3. Jelena Kusakina
4. Antoine Larrieu
5. Katarzyna Knop
6. Nisha Joy
7. Friedrich Breidenbach
8. Anna V Sherwood
9. Geoffrey J Barton
10. Sebastian M Fica
11. Brendan H Davies
12. Gordon G Simpson

• Curated by eLife

  eLife assessment

  This is an important paper reporting that an adenosine methyltransferase in the model plant Arabidopsis functions to target a key RNA component of the spliceosome, as in fission yeast, and thereby contributes to intron recognition. By contrast, the authors report no major role for the methyltransferase in targeting mRNAs, as reported in previous studies in Arabidopsis. While some of the evidence is convincing, other evidence is incomplete. The conclusions that mRNAs are not a significant target and that specific intronic sequences define sensitivity to the methyltransferase require additional support.

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A cryogenic, coincident fluorescence, electron, and ion beam microscope

1. Daan B Boltje
2. Jacob P Hoogenboom
3. Arjen J Jakobi
4. Grant J Jensen
5. Caspar TH Jonker
6. Max J Kaag
7. Abraham J Koster
8. Mart GF Last
9. Cecilia de Agrela Pinto
10. Jürgen M Plitzko
11. Stefan Raunser
12. Sebastian Tacke
13. Zhexin Wang
14. Ernest B van der Wee
15. Roger Wepf
16. Sander den Hoedt

• Curated by eLife

  eLife assessment

  This paper is of particular interest to researchers who plan to use focused-ion beam scanning electron microscopes (FIB-SEMs) and require fluorescent data to guide the milling process. The authors describe a valuable after-market upgrade that allows fluorescent data acquisition during FIB-milling without stage repositioning. Technical details of the fluorescent module upgrade together with the sample stage redesign are compellingly documented and will enhance the implementation of this important technology.

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The anatomy of transcriptionally active chromatin loops in Drosophila primary spermatocytes using super-resolution microscopy

1. Madeleine L. Ball
2. Stefan A. Koestler
3. Leila Muresan
4. Sohaib Abdul Rehman
5. Kevin O’Holleran
6. Robert White

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Structure and flexibility of the yeast NuA4 histone acetyltransferase complex

1. Stefan A Zukin
2. Matthew R Marunde
3. Irina K Popova
4. Katarzyna M Soczek
5. Eva Nogales
6. Avinash B Patel

• Curated by eLife

  eLife assessment

  This manuscript provides insights into the architecture of the yeast histone acetyltransferase complex NuA4 and is of broad interest to those studying transcription and chromatin modification. The cryo-EM data are of very high quality, and enable the authors to devise a structural model that is in much better agreement with biochemical data than previously reported models. This structure represents an important puzzle piece towards a molecular understanding of chromatin modification.

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