RT Journal
A1 Arpat, Alaaddin Bulak
A1 Liechti, Angélica
A1 De Matos, Mara
A1 Dreos, René
A1 Janich, Peggy
A1 Gatfield, David
T1 Transcriptome-wide sites of collided ribosomes reveal principles of translational pausing
JF Genome Research 
JO Genome Research 
YR 2020 
FD July 01 
VO 30 
IS 7 
SP 985 
OP 999 
DO 10.1101/gr.257741.119 
UL http://genome.cshlp.org/content/30/7/985.abstract 
AB 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 translation rate, trapping ∼10% of translating ribosomes in the disome state. A distinct class of pause sites is indicative of deterministic 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.