Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.
Suzanne R Lee, Gabriel A Pratt, Fernando J Martinez, Gene W Yeo, Jens Lykke-Andersen
Molecular cell · 2015 · Vol. 59 (3) · pp. 413-25
Abstract
RNA quality-control pathways get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the adenosine triphosphatase (ATPase) cycle of the SF1 helicase Upf1 is required for mRNA discrimination during nonsense-mediated decay (NMD). Mutations affecting the Upf1 ATPase cycle disrupt the mRNA selectivity of Upf1, leading to indiscriminate accumulation of NMD complexes on both NMD target and non-target mRNAs. In addition, two modulators of NMD-translation and termination codon-proximal poly(A) binding protein-depend on the ATPase activity of Upf1 to limit Upf1-non-target association. Preferential ATPase-dependent dissociation of Upf1 from non-target mRNAs in vitro suggests that selective release of Upf1 contributes to the ATPase dependence of Upf1 target discrimination. Given the prevalence of helicases in RNA regulation, ATP hydrolysis may be a widely used activity in target RNA discrimination.
Linked datasets 3
Target discrimination in nonsense-mediated mRNA decay requires Upf1 ATPase activity (CLIP-Seq)
Homo sapiens
13 data files
| File | Type | Size |
|---|---|---|
| FJM_W1_NoIndex_L001_R1.fastq.gz | OTHER | 4.6 GB |
| FM_UPF_1_NoIndex_L004_R1.fastq.gz | OTHER | 6.5 GB |
| FM_UPF_2_NoIndex_L005_R1.fastq.gz | OTHER | 6.8 GB |
| FM_UPF_3_NoIndex_L006_R1.fastq.gz | OTHER | 7.7 GB |
| FM_UPF_4_NoIndex_L007_R1.fastq.gz | OTHER | 6.8 GB |
| SRR2051421_GSM1704214 | OTHER | 4.6 GB |
| SRR2051422_GSM1704215 | OTHER | 6.5 GB |
| SRR2051423_GSM1704216 | OTHER | 6.8 GB |
| SRR2051424_GSM1704217 | OTHER | 7.7 GB |
| SRR2051425 | OTHER | 6.8 GB |
| SRR2051425_GSM1704218 | OTHER | 6.8 GB |
| SRR2051426_GSM1704219 | OTHER | 6.5 GB |
| WT_NoIndex_L006_R1.fastq.gz | OTHER | 6.5 GB |
Target discrimination in nonsense-mediated mRNA decay requires Upf1 ATPase activity
Homo sapiens
Target discrimination in nonsense-mediated mRNA decay requires Upf1 ATPase activity (RIP-Seq)
Homo sapiens
20 data files
| File | Type | Size |
|---|---|---|
| D-in_AGCGATAG-TATAGCCT_L001_R1.fastq.gz | RIP-Seq | 1.7 GB |
| D-IP_ATTACTCG-ATAGAGGC_L001_R1.fastq.gz | RIP-Seq | 5.3 GB |
| F-in_TAATGCGC-TATAGCCT_L004_R1.fastq.gz | RIP-Seq | 497.7 MB |
| F-IP_CGGCTATG-TATAGCCT_L007_R1.fastq.gz | RIP-Seq | 317.5 MB |
| K-in_TCCGGAGA-ATAGAGGC_L001_R1.fastq.gz | RIP-Seq | 1.6 GB |
| K-IP_CGCTCATT-ATAGAGGC_L001_R1.fastq.gz | RIP-Seq | 1.0 GB |
| SRR2051427 | RIP-Seq | 1.7 GB |
| SRR2051427_GSM1704220 | RIP-Seq | 1.7 GB |
| SRR2051428_GSM1704221 | RIP-Seq | 5.3 GB |
| SRR2051429_GSM1704222 | RIP-Seq | 497.0 MB |
| SRR2051430_GSM1704223 | RIP-Seq | 317.0 MB |
| SRR2051431_GSM1704224 | RIP-Seq | 1.6 GB |
| SRR2051432 | RIP-Seq | 1.0 GB |
| SRR2051432_GSM1704225 | RIP-Seq | 1.0 GB |
| SRR2051433 | RIP-Seq | 1.1 GB |
| SRR2051433_GSM1704226 | RIP-Seq | 1.1 GB |
| SRR2051434 | RIP-Seq | 508.1 MB |
| SRR2051434_GSM1704227 | RIP-Seq | 508.0 MB |
| W-in_TCCGCGAA-TATAGCCT.fastq.gz | RIP-Seq | 1.1 GB |
| W-IP_TCTCGCGC-TATAGCCT_L001_R1.fastq.gz | RIP-Seq | 508.1 MB |
Potentially related datasets 1
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
Analysis pipelines 3
| Pipeline | Assay | Steps | Dataset |
|---|---|---|---|
| GSE69584 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 8 | GSE69584 |
| GSE69585 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 5 | GSE69585 |
| GSE69586 CLIP-seq Data Processing geo_data_processing | CLIP-seq | 8 | GSE69586 |
Funding 9 grants
| Grant | Funder |
|---|---|
| R01 HG004659 | NHGRI NIH HHS (United States) |
| T32 GM008666 | NIGMS NIH HHS (United States) |
| U54 HG007005 | NHGRI NIH HHS (United States) |
| R01 NS075449 | NINDS NIH HHS (United States) |
| HG004659 | NHGRI NIH HHS (United States) |
| NS075449 | NINDS NIH HHS (United States) |
| HG007005 | NHGRI NIH HHS (United States) |
| R01 GM084317 | NIGMS NIH HHS (United States) |
| R01 GM099717 | NIGMS NIH HHS (United States) |