Source 1primary paper2018Proceedings of the National Academy of Sciences
Toolkit/main ORF
main ORF
Also known as: mORF
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The main ORF (mORF) is the protein-coding open reading frame in a transcript whose translation can be repressed by upstream ORFs (uORFs). In Arabidopsis, transcripts initiated from downstream alternative transcription start sites can bypass uORFs and thereby support expression of the mORF, including in blue-light-responsive genes.
Usefulness & Problems
Why this is useful
This RNA regulatory context is useful for understanding how transcript architecture controls protein output from the primary coding sequence. The cited Arabidopsis study indicates that downstream transcription start site selection can relieve uORF-mediated repression of mORF expression in 220 genes under blue light.
Problem solved
It addresses the problem that uORFs can suppress translation of the main coding sequence or promote transcript loss through nonsense-mediated mRNA decay. Alternative transcription start site usage downstream of uORFs provides a route for transcripts to evade these inhibitory effects.
Problem links
Need tighter control over protein production
DerivedThe main ORF (mORF) is the protein-coding open reading frame in transcripts whose translation can be suppressed by upstream ORFs (uORFs). In Arabidopsis, selection of transcription start sites downstream of uORFs enables transcripts to evade uORF-mediated repression and support higher expression of light-regulated genes.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level RNA part used inside a larger architecture that realizes a mechanism.
Mechanisms
alternative transcription start site selectionalternative transcription start site selectionnonsense-mediated mrna decaynonsense-mediated mrna decaytranslation controlTranslation Controluorf-mediated inhibition of main orf translationuorf-mediated inhibition of main orf translationTechniques
No technique tags yet.
Target processes
translationImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
The relevant design feature is transcript initiation relative to uORFs: transcription start sites downstream of uORFs generate mRNAs that avoid uORF-mediated repression of the mORF. The supplied evidence specifically concerns Arabidopsis genes and a blue-light-associated shift in transcription start site usage; no additional construct, delivery, or expression-system details are provided.
The evidence is limited to one Arabidopsis-focused study and describes the mORF as a regulated transcript feature rather than an engineered tool. Quantitative performance, portability to other organisms, and implementation as a generalizable synthetic element are not established by the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Transcripts from TSSs upstream of uORFs accumulated in an NMD mutant for 45 of the 220 genes, including HY5.
We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including <i>HY5</i>, accumulated in a mutant of NMD.
genes with upstream TSS transcript accumulation in NMD mutant 45total genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light enhances transcription from transcription start sites located downstream of uORFs in 220 genes.
Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure.
genes with enhanced downstream TSS usage 220
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Blue light controls gene expression not only by enhancing transcription but also by choosing transcription start sites, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.
Approval Evidence
1 source1 linked approval claimfirst-pass slug main-orf
some transcripts have upstream ORFs (uORFs) that take precedence over the main ORF (mORF) encoding proteins
Source:
mechanistic claimsupports
uORFs often inhibit translation of the main ORF or trigger nonsense-mediated mRNA decay.
The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD).
Source:
Comparisons
Source-backed strengths
The evidence links mORF regulation to two defined post-transcriptional constraints: uORF-mediated translational inhibition and nonsense-mediated mRNA decay. The reported response is gene-scale in Arabidopsis, with blue light enhancing downstream transcription start site usage in 220 genes and NMD-sensitive upstream-uORF-containing transcripts observed for 45 of those genes, including HY5.
Compared with photo-caged mRNA
main ORF and photo-caged mRNA address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation control, translation_control
Strengths here: looks easier to implement in practice.
Compared with tet-controlled riboregulatory module
main ORF and tet-controlled riboregulatory module address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation control, translation_control
Strengths here: looks easier to implement in practice.
Compared with wavelength-selective photo-cage pair for mRNA
main ORF and wavelength-selective photo-cage pair for mRNA address a similar problem space because they share translation.
Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation control, translation_control
Strengths here: looks easier to implement in practice.
Ranked Citations
- 1.