|
| Status |
Public on Apr 12, 2016 |
| Title |
A coding sequence-embedded principle governs translational reading frame fidelity |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Upon initiation at an AUG start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. Although some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known how the ribosome normally prevents spontaneous frameshift errors. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3’ end of 18S rRNA to scan the AUG-like codons after the decoding process. The internal mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a post-decoding mechanism to safeguard the ribosome in the correct reading frame. Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors. Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes codon “stickiness”. Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes by minimizing the appearance of AUG-like codons in the frame 2. These results suggest an important layer of information embedded within the protein coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.
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| |
|
| Overall design |
Investigating the role of 18S rRNA in controlling translational reading frame fidelity
|
| |
|
| Contributor(s) |
Wan J, Gao X, Mao Y, Dong L, Jia L, Zhang X, Qian S |
| Citation(s) |
31549036 |
| |
| Submission date |
Apr 11, 2016 |
| Last update date |
Oct 01, 2019 |
| Contact name |
Ji Wan |
| E-mail(s) |
jw896@cornell.edu
|
| Organization name |
Cornell University
|
| Street address |
303 Biotech 526 Campus Road
|
| City |
Ithaca |
| State/province |
NY |
| ZIP/Postal code |
14853 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (7)
|
| GSM2113583 |
Ribo-Seq (MEF cells, mutant 18S rRNA) |
| GSM2113584 |
Ribo-Seq (HEK393T, control sample for Methionine Starvation) |
| GSM2113585 |
Ribo-Seq (HEK393T, Methionine Starvation) |
| GSM2113586 |
RNA-Seq (MEF cells) |
|
| Relations |
| BioProject |
PRJNA318051 |
| SRA |
SRP073116 |
| SRA |
SRP073116 |
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