A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay.
The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly(A) tail (and thus of PABPC1) is a critica...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797091526196592640 |
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| author | Behm-Ansmant, I Gatfield, D Rehwinkel, J Hilgers, V Izaurralde, E |
| author_facet | Behm-Ansmant, I Gatfield, D Rehwinkel, J Hilgers, V Izaurralde, E |
| author_sort | Behm-Ansmant, I |
| collection | OXFORD |
| description | The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly(A) tail (and thus of PABPC1) is a critical determinant for PTC definition in Drosophila melanogaster. Indeed, tethering of PABPC1 downstream of a PTC abolishes NMD. Conversely, natural stops trigger NMD when the length of the 3' UTR is increased. However, many endogenous transcripts with exceptionally long 3' UTRs escape NMD, suggesting that the increase in 3' UTR length has co-evolved with the acquisition of features that suppress NMD. We provide evidence for the existence of 3' UTRs conferring immunity to NMD. We also show that PABPC1 binding is sufficient for PTC recognition, regardless of cleavage or polyadenylation. The role of PABPC1 in NMD must go beyond that of providing positional information for PTC definition, because its depletion suppresses NMD under conditions in which translation efficiency is not affected. These findings reveal a conserved role for PABPC1 in mRNA surveillance. |
| first_indexed | 2024-03-07T03:34:21Z |
| format | Journal article |
| id | oxford-uuid:bbc99ee5-d06a-44ae-a15b-cc70a1982e0f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:34:21Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:bbc99ee5-d06a-44ae-a15b-cc70a1982e0f2022-03-27T05:19:29ZA conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bbc99ee5-d06a-44ae-a15b-cc70a1982e0fEnglishSymplectic Elements at Oxford2007Behm-Ansmant, IGatfield, DRehwinkel, JHilgers, VIzaurralde, EThe nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs with premature translation termination codons (PTCs). The mechanisms by which PTCs and natural stop codons are discriminated remain unclear. We show that the position of stops relative to the poly(A) tail (and thus of PABPC1) is a critical determinant for PTC definition in Drosophila melanogaster. Indeed, tethering of PABPC1 downstream of a PTC abolishes NMD. Conversely, natural stops trigger NMD when the length of the 3' UTR is increased. However, many endogenous transcripts with exceptionally long 3' UTRs escape NMD, suggesting that the increase in 3' UTR length has co-evolved with the acquisition of features that suppress NMD. We provide evidence for the existence of 3' UTRs conferring immunity to NMD. We also show that PABPC1 binding is sufficient for PTC recognition, regardless of cleavage or polyadenylation. The role of PABPC1 in NMD must go beyond that of providing positional information for PTC definition, because its depletion suppresses NMD under conditions in which translation efficiency is not affected. These findings reveal a conserved role for PABPC1 in mRNA surveillance. |
| spellingShingle | Behm-Ansmant, I Gatfield, D Rehwinkel, J Hilgers, V Izaurralde, E A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title | A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title_full | A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title_fullStr | A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title_full_unstemmed | A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title_short | A conserved role for cytoplasmic poly(A)-binding protein 1 (PABPC1) in nonsense-mediated mRNA decay. |
| title_sort | conserved role for cytoplasmic poly a binding protein 1 pabpc1 in nonsense mediated mrna decay |
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