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Structure and conformational plasticity of the U6 small nuclear ribonucleoprotein core.

Montemayor EJ, Didychuk AL, Liao H, Hu P, Brow DA, Butcher SE
Acta Crystallogr D Struct Biol 73 1-8 (2017)
Cited: 9 times
EuropePMC logo PMID: 28045380

Abstract

U6 small nuclear RNA (snRNA) is a key component of the active site of the spliceosome, a large ribonucleoprotein complex that catalyzes the splicing of precursor messenger RNA. Prior to its incorporation into the spliceosome, U6 is bound by the protein Prp24, which facilitates unwinding of the U6 internal stem-loop (ISL) so that it can pair with U4 snRNA. A previously reported crystal structure of the `core' of the U6 small nuclear ribonucleoprotein (snRNP) contained an ISL-stabilized A62G mutant of U6 bound to all four RNA-recognition motif (RRM) domains of Prp24 [Montemayor et al. (2014), Nature Struct. Mol. Biol. 21, 544-551]. The structure revealed a novel topology containing interlocked rings of protein and RNA that was not predicted by prior biochemical and genetic data. Here, the crystal structure of the U6 snRNP core with a wild-type ISL is reported. This complex crystallized in a new space group, apparently owing in part to the presence of an intramolecular cross-link in RRM1 that was not observed in the previously reported U6-A62G structure. The structure exhibits the same protein-RNA interface and maintains the unique interlocked topology. However, the orientation of the wild-type ISL is altered relative to the A62G mutant structure, suggesting inherent structural dynamics that may facilitate its pairing with U4. Consistent with their similar architectures in the crystalline state, the wild-type and A62G variants of U6 exhibit similar Prp24-binding affinities and electrophoretic mobilities when analyzed by gel-shift assay.

Articles - 5tf6 mentioned but not cited (3)

  1. Structure and conformational plasticity of the U6 small nuclear ribonucleoprotein core. Montemayor EJ, Didychuk AL, Liao H, Hu P, Brow DA, Butcher SE. Acta Crystallogr D Struct Biol 73 1-8 (2017)
  2. A comparative analysis of machine learning classifiers for predicting protein-binding nucleotides in RNA sequences. Agarwal A, Singh K, Kant S, Bahadur RP. Comput Struct Biotechnol J 20 3195-3207 (2022)
  3. Comparative Study of Single-stranded Oligonucleotides Secondary Structure Prediction Tools. Binet T, Padiolleau-Lefèvre S, Octave S, Avalle B, Maffucci I. BMC Bioinformatics 24 422 (2023)


Reviews citing this publication (2)

  1. The life of U6 small nuclear RNA, from cradle to grave. Didychuk AL, Butcher SE, Brow DA. RNA 24 437-460 (2018)
  2. Tools for the cryo-EM gold rush: going from the cryo-EM map to the atomistic model. Kim DN, Sanbonmatsu KY. Biosci Rep 37 BSR20170072 (2017)

Articles citing this publication (4)

  1. Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1. Nomura Y, Roston D, Montemayor EJ, Cui Q, Butcher SE. Nucleic Acids Res 46 11488-11501 (2018)
  2. Architecture of the U6 snRNP reveals specific recognition of 3'-end processed U6 snRNA. Montemayor EJ, Didychuk AL, Yake AD, Sidhu GK, Brow DA, Butcher SE. Nat Commun 9 1749 (2018)
  3. Thermodynamic examination of pH and magnesium effect on U6 RNA internal loop. O'Connell AA, Hanson JA, McCaskill DC, Moore ET, Lewis DC, Grover N. RNA 25 1779-1792 (2019)
  4. Defining essential elements and genetic interactions of the yeast Lsm2-8 ring and demonstration that essentiality of Lsm2-8 is bypassed via overexpression of U6 snRNA or the U6 snRNP subunit Prp24. Roth AJ, Shuman S, Schwer B. RNA 24 853-864 (2018)


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