A [Cu]rious Ribosomal Profiling Pattern Leads to the Discovery of Ribosomal Frameshifting in the Synthesis of a Copper Chaperone

Atkins, John F.; Loughran, Gary; Baranov, Pavel V.

doi:10.1016/j.molcel.2017.01.002

Cited by 4 publications

(4 citation statements)

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“…reported the discovery and functional characterization of efficient ribosomal frameshifting in the Escherichia coli ( E. coli ) copA gene ( Meydan et al., 2017 ). This finding is well supported by external ribosome profiling data that prompted their investigation ( Li et al., 2014 ; Atkins et al., 2017 ) and was subsequently confirmed by an independent study ( Drees et al., 2017 ). Along with this important discovery, the authors reported that ribosomal frameshifting occurs in the APT7B gene, which is a human ortholog of copA .…”

Section: Introductionsupporting

confidence: 67%

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

Loughran

Fedorova²,

Khan³

et al. 2022

Molecular Cell

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Section: Introductionsupporting

confidence: 67%

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

Loughran

Fedorova²,

Khan³

et al. 2022

Molecular Cell

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“…One type of recoding and splicing are alternatively used in different occurrences of one set of othologs ( 74 – 76 ), in several instances one type of recoding has been replaced by a different type ( 16 ). One example of the latter is dnaX where in E. coli expression of a second protein product involves a ribosomal frameshift event and in other bacteria including Thermus thermophilus , synthesis of the counterpart product involves transcription slippage ( 20 , 77 – 79 ).…”

Section: Discussionmentioning

confidence: 99%

Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis

Penno

Kumari

Baranov

et al. 2017

Nucleic Acids Research

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Synthesis of HIV GagPol involves a proportion of ribosomes translating a U6A shift site at the distal end of the gag gene performing a programmed -1 ribosomal frameshift event to enter the overlapping pol gene. In vitro studies here show that at the same shift motif HIV reverse transcriptase generates -1 and +1 indels with their ratio being sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5′ adjacent base. The GGG sequence 3′ adjacent to the U6A shift/slippage site, which is important for ribosomal frameshifting, is shown here to limit reverse transcriptase base substitution and indel ‘errors’ in the run of A’s in the product. The indels characterized here have either 1 more or less A, than the corresponding number of template U’s. cDNA with 5 A’s may yield novel Gag product(s), while cDNA with an extra base, 7 A’s, may only be a minor contributor to GagPol polyprotein. Synthesis of a proportion of non-ribosomal frameshift derived GagPol would be relevant in efforts to identify therapeutically useful compounds that perturb the ratio of GagPol to Gag, and pertinent to the extent in which specific polymerase slippage is utilized in gene expression.

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“…Another translation pattern is stop-codon read-through which we have described in the nervous system (Figure 3; von der Haar and Tuite, 2007;Jungreis et al, 2016;Li and Zhang, 2019). Ribosome profiling can also analyze frameshift mutations in the main open reading frame, although it has not been remarkably successful (Atkins et al, 2017).…”

Section: Applications Of Translatomics In Other Fieldsmentioning

confidence: 99%

Insights Into Translatomics in the Nervous System

et al. 2020

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Most neurological disorders are caused by abnormal gene translation. Generally, dysregulation of elements involved in the translational process disrupts homeostasis in neurons and neuroglia. Better understanding of how the gene translation process occurs requires detailed analysis of transcriptomic and proteomic profile data. However, a lack of strictly direct correlations between mRNA and protein levels limits translational investigation by combining transcriptomic and proteomic profiling. The much better correlation between proteins and translated mRNAs than total mRNAs in abundance and insufficiently sensitive proteomics approach promote the requirement of advances in translatomics technology. Translatomics which capture and sequence the mRNAs associated with ribosomes has been effective in identifying translational changes by genetics or projections, ribosome stalling, local translation, and transcript isoforms in the nervous system. Here, we place emphasis on the main three translatomics methods currently used to profile mRNAs attached to ribosome-nascent chain complex (RNC-mRNA). Their prominent applications in neurological diseases including glioma, neuropathic pain, depression, fragile X syndrome (FXS), neurodegenerative disorders are outlined. The content reviewed here expands our understanding on the contributions of aberrant translation to neurological disease development.

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A [Cu]rious Ribosomal Profiling Pattern Leads to the Discovery of Ribosomal Frameshifting in the Synthesis of a Copper Chaperone

Cited by 4 publications

References 11 publications

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis

Insights Into Translatomics in the Nervous System

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