Specificity of ribonucleoprotein interaction determined by RNA folding during complex formation

Allain, Frédéric H.‐T.; Gubser, Charles C.; Howe, Peter W.A.; Nagai, Kiyoshi; Neuhaus, David; Varani, Gabriele

doi:10.1038/380646a0

Cited by 258 publications

(275 citation statements)

References 27 publications

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“…Structural studies revealed that the ability of the helix to bend at the bulged nucleotides is critical for protein binding. The RRM-containing U1A protein binds to the U1 snRNA and to its own pre-mRNA (Oubridge et al 1994;Allain et al 1996) by recognizing 6 unpaired nucleotides in a sequence-specific manner (Hall 1994). The high sequence conservation of the bulged nucleotides of the TLC1 RNA bulged stem and the importance of an intact stem suggest that Est1p could recognize this structure, at least in part, in a similar manner.…”

Section: How Might Est1p Interact With the Bulged Stem?mentioning

confidence: 98%

A bulged stem tethers Est1p to telomerase RNA in budding yeast

Seto

Livengood²,

Tzfati³

et al. 2002

Genes Dev.

131

151

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It is well established that the template for telomeric DNA synthesis is provided by the RNA subunit of telomerase; however, the additional functions provided by most of the rest of the RNA (>1000 nucleotides in budding yeast) are largely unknown. By alignment of telomerase RNAs of Saccharomyces cerevisiae and six Kluyveromyces species followed by mutagenesis of the S. cerevisiae RNA, we found a conserved region that is essential for telomere maintenance. Phylogenetic analysis and computer folding revealed that this region is conserved not only in primary nucleotide sequence but also in secondary structure. A common bulged-stem structure was predicted in all seven yeast species. Mutational analysis showed the structure to be essential for telomerase function. Suppression of bulged-stem mutant phenotypes by overexpression of Est1p and loss of co-immunoprecipitation of the mutant RNAs with Est1p indicated that this bulged stem is necessary for association of Est1p, a telomerase regulatory subunit. Est1p in yeast extract bound specifically to a small RNA containing the bulged stem, suggesting a direct interaction. We propose that this RNA structure links the enzymatic core of telomerase with Est1p, thereby allowing Est1p to recruit or activate telomerase at the telomere.

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Section: How Might Est1p Interact With the Bulged Stem?mentioning

confidence: 98%

A bulged stem tethers Est1p to telomerase RNA in budding yeast

Seto

Livengood²,

Tzfati³

et al. 2002

Genes Dev.

131

151

View full text Add to dashboard Cite

show abstract

“…However, it was later shown that RRMs can contain supplementary secondary structures that are important for proper folding or RNA binding. For example, the structure of the U1A RRM in complex with RNA showed that this domain possesses an additional helix α 3 at its C-terminus that interacts with the β-sheet surface of the RRM in its free form but rotates away from the β-sheet when the RRM is in complex with RNA [2]. Although this helix is not directly involved in RNA binding, it was…”

Section: Protein Productionmentioning

confidence: 99%

“…Many RNA binding proteins have been purified using a combination of ion exchange chromatography and size-exclusion chromatography [2,12,18,22,36,46].…”

Section: Purification Of Rna Binding Proteinsmentioning

confidence: 99%

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Structure determination and dynamics of protein–RNA complexes by NMR spectroscopy

Dominguez

Schubert

Duss

et al. 2011

Progress in Nuclear Magnetic Resonance Spectroscopy

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“…The U1A protein tertiary structure has been obtained in solution in complex with one of its specific RNA, the PIE from its pre-mRNA [19,42]. The determinants for binding have been analyzed in detail and compared with those of the previously known crystal complex with stem-loop II from U1-snRNA [43].…”

Section: Binding Specificity Of U1amentioning

confidence: 99%

Prediction of a new class of RNA recognition motif

Cerdà-Costa¹,

Bonet²,

Fernández³

et al. 2010

J Mol Model

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The observation that activation domains (AD) of procarboxypeptidases are rather long, compared to pro-regions of other zymogens, points out the possibility that they could play additional roles apart from precluding enzymatic activity within the proenzyme and helping in its folding process. In the present work, we have compared the overall pro-domain tertiary structure with several proteins belonging to the same fold in SCOP by using structure and sequence comparisons. The best score has been obtained between the activation domain of the human procarboxypeptidase A4 (ADA4h) and the human U1A protein from the U1 snRNP.Structural alignment has revealed the existence of RNP1-and RNP2-related sequences in ADA4h. After modeling ADA4h on U1A, the new structure was used to extract a new sequence pattern characteristic for important residues at key positions. The new sequence pattern allowed scanning protein sequences to predict the RNA-binding function for 32 sequences undetected by PFAM. Unspecific RNA EMSA experimentally supported the prediction that ADA4h binds an RNA motif similar to the U1A binding-motif of stem-loop II of U1 small nuclear RNA. The experiments carried out with ADA4h in the present work Manuscript Click here to download Manuscript: JMMO1391R2_final.doc 2 suggest the sharing of a common ancestor with other RRMs. However, the fact that key residues preventing activity within the proenzyme are also key residues for RNA binding might induce the activation domains of procarboxypeptidases to evolve from the canonical RNP1 and 2 sequences.

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Specificity of ribonucleoprotein interaction determined by RNA folding during complex formation

Cited by 258 publications

References 27 publications

A bulged stem tethers Est1p to telomerase RNA in budding yeast

A bulged stem tethers Est1p to telomerase RNA in budding yeast

Structure determination and dynamics of protein–RNA complexes by NMR spectroscopy

Prediction of a new class of RNA recognition motif

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