Transcriptome-wide sites of collided ribosomes reveal principles of translational pausing

被引:62
作者
Arpat, Alaaddin Bulak [1 ,2 ]
Liechti, Angelica [1 ]
De Matos, Mara [1 ]
Dreos, Rene [1 ,2 ]
Janich, Peggy [1 ]
Gatfield, David [1 ]
机构
[1] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland
[2] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland
基金
瑞士国家科学基金会;
关键词
MESSENGER-RNA; PROFILING REVEALS; ELONGATION; MEMBRANE; EFFICIENCY; MECHANISM; DYNAMICS; PROMOTES; CODONS;
D O I
10.1101/gr.257741.119
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Translation initiation is the major regulatory step defining the rate of protein production from an mRNA. Meanwhile, the impact of nonuniform ribosomal elongation rates is largely unknown. Using a modified ribosome profiling protocol based on footprints from two closely packed ribosomes (disomes), we have mapped ribosomal collisions transcriptome-wide in mouse liver. We uncover that the stacking of an elongating onto a paused ribosome occurs frequently and scales with trans-lation rate, trapping similar to 10% of translating ribosomes in the disome state. A distinct class of pause sites is indicative of deter-ministic pausing signals. Pause site association with specific amino acids, peptide motifs, and nascent polypeptide structure is suggestive of programmed pausing as a widespread mechanism associated with protein folding. Evolutionary conservation at disome sites indicates functional relevance of translational pausing. Collectively, our disome profiling approach allows unique insights into gene regulation occurring at the step of translation elongation.
引用
收藏
页码:985 / 999
页数:15
相关论文
共 44 条
  • [1] Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes
    Andreev, Dmitry E.
    O'Connor, Patrick B. F.
    Zhdanov, Alexander V.
    Dmitriev, Ruslan I.
    Shatsky, Ivan N.
    Papkovsky, Dmitri B.
    Baranov, Pavel V.
    [J]. GENOME BIOLOGY, 2015, 16
  • [2] Positively Charged Residues Are the Major Determinants of Ribosomal Velocity
    Charneski, Catherine A.
    Hurst, Laurence D.
    [J]. PLOS BIOLOGY, 2013, 11 (03):
  • [3] Determinants of Translation Elongation Speed and Ribosomal Profiling Biases in Mouse Embryonic Stem Cells
    Dana, Alexandra
    Tuller, Tamir
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2012, 8 (11)
  • [4] Translational Control through Differential Ribosome Pausing during Amino Acid Limitation in Mammalian Cells
    Darnell, Alicia M.
    Subramaniam, Arvind R.
    O'Shea, Erin K.
    [J]. MOLECULAR CELL, 2018, 71 (02) : 229 - +
  • [5] The extent of ribosome queuing in budding yeast
    Diament, Alon
    Feldman, Anna
    Schochet, Elisheva
    Kupiec, Martin
    Arava, Yoav
    Tuller, Tamir
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2018, 14 (01)
  • [6] Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding
    Doering, Kristina
    Ahmed, Nabeel
    Riemer, Trine
    Suresh, Harsha Garadi
    Vainshtein, Yevhen
    Habich, Markus
    Riemer, Jan
    Mayer, Matthias P.
    O'Brien, Edward P.
    Kramer, Guenter
    Bukau, Bernd
    [J]. CELL, 2017, 170 (02) : 298 - +
  • [7] The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation
    Duc, Khanh Dao
    Song, Yun S.
    [J]. PLOS GENETICS, 2018, 14 (01):
  • [8] Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast
    Gamble, Caitlin E.
    Brule, Christina E.
    Dean, Kimberly M.
    Fields, Stanley
    Grayhack, Elizabeth J.
    [J]. CELL, 2016, 166 (03) : 679 - 690
  • [9] Integration of microRNA miR-122 in hepatic circadian gene expression
    Gatfield, David
    Le Martelot, Gwendal
    Vejnar, Charles E.
    Gerlach, Daniel
    Schaad, Olivier
    Fleury-Olela, Fabienne
    Ruskeepaa, Anna-Liisa
    Oresic, Matej
    Esau, Christine C.
    Zdobnov, Evgeny M.
    Schibler, Ueli
    [J]. GENES & DEVELOPMENT, 2009, 23 (11) : 1313 - 1326
  • [10] Robust landscapes of ribosome dwell times and aminoacyl-tRNAs in response to nutrient stress in liver
    Gobet, Cedric
    Weger, Benjamin Dieter
    Marquis, Julien
    Martin, Eva
    Neelagandan, Nagammal
    Gachon, Frederic
    Naef, Felix
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (17) : 9630 - 9641