Molecular Cell
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Apr 06, 2017

Volume 66Issue 1p1-162
Open Archive
On the cover: The histone variant H2A.L.2 directs the loading of transition proteins onto chromatin, which in turn allows the processing and assembly of protamines. In this issue, Barral et al. (pp. 89–101) show that in the absence of H2A.L.2, transition proteins are mis-localized (in red), but the protamine-mediated histone replacement takes place, leading to defective chromatin compaction in spermatozoa. Credit: Delphine Beltran-Khochbin....
On the cover: The histone variant H2A.L.2 directs the loading of transition proteins onto chromatin, which in turn allows the processing and assembly of protamines. In this issue, Barral et al. (pp. 89–101) show that in the absence of H2A.L.2, transition proteins are mis-localized (in red), but the protamine-mediated histone replacement takes place, leading to defective chromatin compaction in spermatozoa. Credit: Delphine Beltran-Khochbin.



  • Translation of CircRNAs

    • Nagarjuna Reddy Pamudurti,
    • Osnat Bartok,
    • Marvin Jens,
    • Reut Ashwal-Fluss,
    • Christin Stottmeister,
    • Larissa Ruhe,
    • Mor Hanan,
    • Emanuel Wyler,
    • Daniel Perez-Hernandez,
    • Evelyn Ramberger,
    • Shlomo Shenzis,
    • Moshe Samson,
    • Gunnar Dittmar,
    • Markus Landthaler,
    • Marina Chekulaeva,
    • Nikolaus Rajewsky,
    • Sebastian Kadener
    Pamudurti et al. show that a subset of circRNAs is translated. These circRNAs generally share the start codon with the hosting RNA, encode proteins with specific protein domains, and are translated in a cap-independent manner.
  • Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

    • Ivano Legnini,
    • Gaia Di Timoteo,
    • Francesca Rossi,
    • Mariangela Morlando,
    • Francesca Briganti,
    • Olga Sthandier,
    • Alessandro Fatica,
    • Tiziana Santini,
    • Adrian Andronache,
    • Mark Wade,
    • Pietro Laneve,
    • Nikolaus Rajewsky,
    • Irene Bozzoni
    Legnini et al. identified circ-ZNF609, a circular RNA expressed in murine and human myoblasts, which controls myoblast proliferation. Circ-ZNF609 contains an open reading frame and is translated into a protein in a splicing-dependent/cap-independent manner. Circ-ZNF609 translation can be modulated by stress conditions.
  • Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes

    • Carlo Baejen,
    • Jessica Andreani,
    • Phillipp Torkler,
    • Sofia Battaglia,
    • Bjoern Schwalb,
    • Michael Lidschreiber,
    • Kerstin C. Maier,
    • Andrea Boltendahl,
    • Petra Rus,
    • Stephanie Esslinger,
    • Johannes Söding,
    • Patrick Cramer
    RNA polymerase II undergoes a concerted transition at the 3′ end of protein coding genes. Baejen et al. present a genome-wide analysis of this 3′-transition in budding yeast. They show that this transition requires the Spt5 elongation factor and demonstrate that polymerase II release from DNA requires the Rat1 exonuclease.
  • SNF2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance and Proper Replication

    • Nitika Taneja,
    • Martin Zofall,
    • Vanivilasini Balachandran,
    • Gobi Thillainadesan,
    • Tomoyasu Sugiyama,
    • David Wheeler,
    • Ming Zhou,
    • Shiv I.S. Grewal
    Taneja et al. show that a SNF2 family chromatin remodeler suppresses histone turnover to promote epigenetic transmission of heterochromatin in dividing cells and uncover a mechanism in which suppression of nucleosome turnover at specific genomic sites facilitates proper replication
  • Metazoan Nuclear Pores Provide a Scaffold for Poised Genes and Mediate Induced Enhancer-Promoter Contacts

    • Pau Pascual-Garcia,
    • Brian Debo,
    • Jennifer R. Aleman,
    • Jessica A. Talamas,
    • Yemin Lan,
    • Nha H. Nguyen,
    • Kyoung J. Won,
    • Maya Capelson
    Nuclear pore components (Nups) are known to interact with chromatin, but the precise mechanistic roles of Nups in gene regulation remain incompletely defined. Now, findings from Pascual-Garcia et al. reveal that silent genes can be bound by nuclear pores to promote enhancer-promoter looping upon activation.
  • Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation

    • Ameet Shetty,
    • Scott P. Kallgren,
    • Carina Demel,
    • Kerstin C. Maier,
    • Dan Spatt,
    • Burak H. Alver,
    • Patrick Cramer,
    • Peter J. Park,
    • Fred Winston
    Shetty et al. show that Spt5, a transcription factor conserved in all domains of life, globally regulates transcription by RNA polymerase II in vivo. Spt5 controls the level and rate of RNAPII transcription, its ability to elongate past a barrier, and the synthesis of distinct classes of antisense RNAs.
  • Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells

    • Sophie Barral,
    • Yuichi Morozumi,
    • Hiroki Tanaka,
    • Emilie Montellier,
    • Jérôme Govin,
    • Maud de Dieuleveult,
    • Guillaume Charbonnier,
    • Yohann Couté,
    • Denis Puthier,
    • Thierry Buchou,
    • Fayçal Boussouar,
    • Takashi Urahama,
    • François Fenaille,
    • Sandrine Curtet,
    • Patrick Héry,
    • Nicolas Fernandez-Nunez,
    • Hitoshi Shiota,
    • Matthieu Gérard,
    • Sophie Rousseaux,
    • Hitoshi Kurumizaka,
    • Saadi Khochbin
    Histone-to-protamine transition is essential for procreation, yet its molecular basis has remained obscure. Barral et al. show that a histone variant, H2A.L.2, directs the transformation of nucleosomes by allowing the loading onto chromatin of non-histone transition proteins, which in turn control the final genome organization and compaction by protamines.
  • The BET Protein BRD2 Cooperates with CTCF to Enforce Transcriptional and Architectural Boundaries

    • Sarah C. Hsu,
    • Thomas G. Gilgenast,
    • Caroline R. Bartman,
    • Christopher R. Edwards,
    • Aaron J. Stonestrom,
    • Peng Huang,
    • Daniel J. Emerson,
    • Perry Evans,
    • Michael T. Werner,
    • Cheryl A. Keller,
    • Belinda Giardine,
    • Ross C. Hardison,
    • Arjun Raj,
    • Jennifer E. Phillips-Cremins,
    • Gerd A. Blobel
    BET family proteins impact gene expression in multiple ways, and they are pharmacologic targets for various diseases. Hsu et al. show that BRD2 is recruited to CTCF sites where it contributes to CTCF boundary formation and enhancer insulation.
  • Plasma Membrane CRPK1-Mediated Phosphorylation of 14-3-3 Proteins Induces Their Nuclear Import to Fine-Tune CBF Signaling during Cold Response

    • Ziyan Liu,
    • Yuxin Jia,
    • Yanglin Ding,
    • Yiting Shi,
    • Zhen Li,
    • Yan Guo,
    • Zhizhong Gong,
    • Shuhua Yang
    How the plasma membrane senses and transduces cold signals remains unknown. Liu et al. demonstrate that the cold-activated plasma membrane CRPK1 phosphorylates 14-3-3 proteins, which are imported from the cytosol to the nucleus and interact with CBF proteins to promote their destabilization, thus fine-tuning CBF-dependent cold signaling.
  • LSM12 and ME31B/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons

    • Jongbo Lee,
    • Eunseok Yoo,
    • Hoyeon Lee,
    • Keunhee Park,
    • Jin-Hoe Hur,
    • Chunghun Lim
    Lee et al. discover that ATAXIN-2 protein complex switches between activator and repressor modes of posttranscriptional regulation via its associating factors LSM12 and ME31B/DDX6. This, in turn, defines PERIOD-dependent and -independent clock functions of ATAXIN-2 that contribute to 24 hr periodicity and high-amplitude rhythms, respectively, in circadian behaviors in Drosophila.
  • Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy

    • Mengjie Hu,
    • Qiang Luo,
    • Gulimiran Alitongbieke,
    • Shuyi Chong,
    • Chenting Xu,
    • Lei Xie,
    • Xiaohui Chen,
    • Duo Zhang,
    • Yuqi Zhou,
    • Zhaokai Wang,
    • Xiaohong Ye,
    • Lijun Cai,
    • Fang Zhang,
    • Huibin Chen,
    • Fuquan Jiang,
    • Hui Fang,
    • Shanjun Yang,
    • Jie Liu,
    • Maria T. Diaz-Meco,
    • Ying Su,
    • Hu Zhou,
    • Jorge Moscat,
    • Xiangzhi Lin,
    • Xiao-kun Zhang
    Hu et al. identified celastrol as a ligand of nuclear receptor Nur77. They uncover an anti-inflammatory mechanism in which celastrol promotes Nur77 migration from the nucleus to mitochondria, where it is ubiquitinated by TRAF2. Ubiquitinated Nur77 then interacts with p62/SQSTM1, leading to autophagy of dysfunctional mitochondria and alleviation of inflammation.

Short Article

  • Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling

    • Xu Xiao,
    • Jing-Jie Tang,
    • Chao Peng,
    • Yan Wang,
    • Lin Fu,
    • Zhi-Ping Qiu,
    • Yue Xiong,
    • Lian-Fang Yang,
    • Hai-Wei Cui,
    • Xiao-Long He,
    • Lei Yin,
    • Wei Qi,
    • Catherine C.L. Wong,
    • Yun Zhao,
    • Bo-Liang Li,
    • Wen-Wei Qiu,
    • Bao-Liang Song
    Xiao et al. identify that SMO is covalently modified by cholesterol. This modification is regulated by Ptch1 and Hh and is essential for Hh signaling. It suggests that Hh signaling transduces to SMO through modulating its cholesterylation and that targeting SMO cholesterylation may provide a therapeutic approach to treat Hh-pathway-related cancers.