Structural basis for cooperative RNA binding and export complex assembly by HIV Rev

Daugherty, Matthew D.; Liu, Bella; Frankel, Alan D.

doi:10.1038/nsmb.1902

Cited by 149 publications

(275 citation statements)

References 40 publications

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“…for Rev-dependent nuclear export through the CRM1 pathway (18). Using either RNA FISH on fixed cells or RT-PCR on subcellular fractions, we detected the presence of introns in the cytoplasm after overexpression of Rev (Fig.…”

Section: Ribosomal Scanning Of Nonspliced Mrnas Gives Rise To Productmentioning

confidence: 99%

Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway

Apcher

Millot

Daskalogianni

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The scanning of maturing mRNAs by ribosomes plays a key role in the mRNA quality control process. When ribosomes first engage with the newly synthesized mRNA, and if peptides are produced, is unclear, however. Here we show that ribosomal scanning of prespliced mRNAs occurs in the nuclear compartment, and that this event produces peptide substrates for the MHC class I pathway. Inserting antigenic peptide sequences in introns that are spliced out before the mRNAs exit the nuclear compartment results in an equal amount of antigenic peptide products as when the peptides are encoded from the main open reading frame (ORF). Taken together with the detection of intron-encoded nascent peptides and RPS6/RPL7-carrying complexes in the perinucleolar compartment, these results show that peptides are produced by a translation event occurring before mRNA splicing. This suggests that ribosomes occupy and scan mRNAs early in the mRNA maturation process, and suggests a physiological role for nuclear mRNA translation, and also helps explain how the immune system tolerates peptides derived from tissue-specific mRNA splice variants.MHC class I restricted antigen presentation | mRNA maturation | nuclear translation R NAs carrying premature termination codons or are recognized as defective in other aspects are prevented from further translation and disposed of by the nonsense-mediated decay (NMD) pathway (1). The detection of premature stop codons is mediated by the scanning ribosome; however, when the ribosomes first engage with the newly synthesized mRNA, and if this event results in the production of peptides, is unclear. Two observations from the field of immunology and the presentation of peptides on MHC class I molecules have highlighted some aspects relevant to the role of the ribosomes in the mRNA maturation process. The first observation is related to the detection of antigenic peptides originating from intron sequences, and the second is related to the observation that the synthesis of antigenic peptide substrates and full-length proteins are two spatiotemporarily distinct events (2-5).The presentation of antigenic peptides on MHC class I molecules allows CD8 + T cells to detect and eliminate cells in which the repertoire of peptide substrates has been altered owing to the presence of viruses or to changes in the presentation of endogenous antigens (6, 7). However, despite the key role of antigen presentation on MHC class I molecules in immune surveillance, the source of peptides for the MHC class I pathway is not yet known. Accumulating evidence indicates that the processing of alternative peptide substrates plays a major role, and that degradation products derived from full-length proteins have limited access to the MHC class I pathway (8-10). We recently demonstrated that pioneer translation products (PTPs) that form antigenic peptide substrates for the MHC class I pathway are produced by a translation event that is distinct from the canonical event giving rise to full-length proteins and does not require the cap-binding ...

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Section: Ribosomal Scanning Of Nonspliced Mrnas Gives Rise To Productmentioning

confidence: 99%

Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway

Apcher

Millot

Daskalogianni

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Dimerization of proteins that bind to RNA is not unprecedented; for example, the Cys 3 His ZF ZAP is a monomer in solution that then dimerizes upon binding to the ZAP-responsive RNA element (34). Other RNA-binding proteins that recognize their targets in a cooperative manner are the human zipcode-binding protein IMP-1, HIV-1 Rev protein, hordeiviral γb protein, human La protein, and tomato bushy stunt virus p33 protein (35)(36)(37)(38). There are also other AUrich RNA-binding proteins such as AUF-1 (p42), Hsp70, and HuR, which bind to their respective RNA partners in a cooperative manner (39)(40)(41).…”

Section: Cpsf30 Contains Ironmentioning

confidence: 99%

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

Shimberg

Michalek

Oluyadi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cleavage and polyadenylation specificity factor 30 (CPSF30) is a key protein involved in pre-mRNA processing. CPSF30 contains five Cys 3 His domains (annotated as "zinc-finger" domains). Using inductively coupled plasma mass spectrometry, X-ray absorption spectroscopy, and UV-visible spectroscopy, we report that CPSF30 is isolated with iron, in addition to zinc. Iron is present in CPSF30 as a 2Fe-2S cluster and uses one of the Cys 3 His domains; 2Fe-2S clusters with a Cys 3 His ligand set are rare and notably have also been identified in MitoNEET, a protein that was also annotated as a zinc finger. These findings support a role for iron in some zinc-finger proteins. Using electrophoretic mobility shift assays and fluorescence anisotropy, we report that CPSF30 selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF30/RNA binding. Removal of zinc, or both zinc and iron, abrogates binding, whereas removal of just iron significantly lessens binding. From these data we propose a model for RNA recognition that involves a metaldependent cooperative binding mechanism.zinc | iron-sulfur | RNA | protein | binding

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“…ARMs are flexible RNA-binding domains that typically confer specificity for particular RNAs by recognizing RNA sequences and/or structures (61,62). For example, the ARM in Rev specifically recognizes and binds its RNA target (63)(64)(65)(66). Critical arginines in the ARM make base-specific contacts with the RNA and are necessary for binding.…”

Section: Discussionmentioning

confidence: 99%

The Nucleic Acid-binding Domain and Translational Repression Activity of a Xenopus Terminal Uridylyl Transferase

Lapointe

Wickens

2013

Journal of Biological Chemistry

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Background: TUT7 adds uridines to and regulates RNAs. Results: Xenopus TUT7 (XTUT7) uridylates RNAs, possesses a basic region that binds nucleic acids, and represses translation of a polyadenylated RNA. Conclusion: XTUT7 contains a nucleic acid-binding domain important for activity and can repress translation. Significance: The basic region of XTUT7 may bind RNA in vivo. XTUT7 may control mRNAs by occluding poly(A).

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Structural basis for cooperative RNA binding and export complex assembly by HIV Rev

Cited by 149 publications

References 40 publications

Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway

Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway

Cleavage and polyadenylation specificity factor 30: An RNA-binding zinc-finger protein with an unexpected 2Fe–2S cluster

The Nucleic Acid-binding Domain and Translational Repression Activity of a Xenopus Terminal Uridylyl Transferase

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