#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Combinatorial Amino Acid Code for RNA Recognition by Pentatricopeptide Repeat Proteins


The pentatricopeptide repeat (PPR) is a helical repeat motif found in an exceptionally large family of RNA–binding proteins that functions in mitochondrial and chloroplast gene expression. PPR proteins harbor between 2 and 30 repeats and typically bind single-stranded RNA in a sequence-specific fashion. However, the basis for sequence-specific RNA recognition by PPR tracts has been unknown. We used computational methods to infer a code for nucleotide recognition involving two amino acids in each repeat, and we validated this model by recoding a PPR protein to bind novel RNA sequences in vitro. Our results show that PPR tracts bind RNA via a modular recognition mechanism that differs from previously described RNA–protein recognition modes and that underpins a natural library of specific protein/RNA partners of unprecedented size and diversity. These findings provide a significant step toward the prediction of native binding sites of the enormous number of PPR proteins found in nature. Furthermore, the extraordinary evolutionary plasticity of the PPR family suggests that the PPR scaffold will be particularly amenable to redesign for new sequence specificities and functions.


Vyšlo v časopise: A Combinatorial Amino Acid Code for RNA Recognition by Pentatricopeptide Repeat Proteins. PLoS Genet 8(8): e32767. doi:10.1371/journal.pgen.1002910
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002910

Souhrn

The pentatricopeptide repeat (PPR) is a helical repeat motif found in an exceptionally large family of RNA–binding proteins that functions in mitochondrial and chloroplast gene expression. PPR proteins harbor between 2 and 30 repeats and typically bind single-stranded RNA in a sequence-specific fashion. However, the basis for sequence-specific RNA recognition by PPR tracts has been unknown. We used computational methods to infer a code for nucleotide recognition involving two amino acids in each repeat, and we validated this model by recoding a PPR protein to bind novel RNA sequences in vitro. Our results show that PPR tracts bind RNA via a modular recognition mechanism that differs from previously described RNA–protein recognition modes and that underpins a natural library of specific protein/RNA partners of unprecedented size and diversity. These findings provide a significant step toward the prediction of native binding sites of the enormous number of PPR proteins found in nature. Furthermore, the extraordinary evolutionary plasticity of the PPR family suggests that the PPR scaffold will be particularly amenable to redesign for new sequence specificities and functions.


Zdroje

1. BochJ, ScholzeH, SchornackS, LandgrafA, HahnS, et al. (2009) Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326: 1509–1512.

2. MoscouMJ, BogdanoveAJ (2009) A simple cipher governs DNA recognition by TAL effectors. Science 326: 1501.

3. LuG, DolgnerSJ, HallTM (2009) Understanding and engineering RNA sequence specificity of PUF proteins. Curr Opin Struct Biol 19: 110–115.

4. CookeA, PriggeA, OppermanL, WickensM (2011) Targeted translational regulation using the PUF protein family scaffold. Proc Natl Acad Sci U S A 108: 15870–15875.

5. DongS, WangY, Cassidy-AmstutzC, LuG, BiglerR, et al. (2011) Specific and modular binding code for cytosine recognition in Pumilio/FBF (PUF) RNA-binding domains. J Biol Chem 286: 26732–26742.

6. SmallI, PeetersN (2000) The PPR motif - a TPR-related motif prevalent in plant organellar proteins. Trends Biochem Sci 25: 46–47.

7. Schmitz-LinneweberC, SmallI (2008) Pentatricopeptide repeat proteins: a socket set for organelle gene expression. Trends Plant Sci 13: 663–670.

8. RuzzenenteB, MetodievMD, WredenbergA, BraticA, ParkCB, et al. (2012) LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. EMBO J 31: 443–456.

9. FujiiS, SmallI (2011) The evolution of RNA editing and pentatricopeptide repeat genes. New Phytol 191: 37–47.

10. FujiiS, BondCS, SmallID (2011) Selection patterns on restorer-like genes reveal a conflict between nuclear and mitochondrial genomes throughout angiosperm evolution. Proc Natl Acad Sci U S A 108: 1723–1728.

11. PfalzJ, BayraktarO, PrikrylJ, BarkanA (2009) Site-specific binding of a PPR protein defines and stabilizes 5′ and 3′ mRNA termini in chloroplasts. EMBO J 28: 2042–2052.

12. PrikrylJ, RojasM, SchusterG, BarkanA (2011) Mechanism of RNA stabilization and translational activation by a pentatricopeptide repeat protein. Proc Natl Acad Sci USA 108: 415–420.

13. MeierhoffK, FelderS, NakamuraT, BechtoldN, SchusterG (2003) HCF152, an Arabidopsis RNA binding pentatricopeptide repeat protein involved in the processing of chloroplast psbB-psbT-psbH-petB-petD RNAs. Plant Cell 15: 1480–1495.

14. OkudaK, ShikanaiT (2012) A pentatricopeptide repeat protein acts as a site-specificity factor at multiple RNA editing sites with unrelated cis-acting elements in plastids. Nucleic Acids Res 40: 5052–5064.

15. KobayashiK, KawabataM, HisanoK, KazamaT, MatsuokaK, et al. (2012) Identification and characterization of the RNA binding surface of the pentatricopeptide repeat protein. Nucleic Acids Res 40: 2712–2723.

16. ZhelyazkovaP, HammaniK, RojasM, VoelkerR, Vargas-SuarezM, et al. (2012) Protein-mediated protection as the predominant mechanism for defining processed mRNA termini in land plant chloroplasts. Nucleic Acids Res 40: 3092–3105.

17. RuweH, Schmitz-LinneweberC (2012) Short non-coding RNA fragments accumulating in chloroplasts: footprints of RNA binding proteins? Nucleic Acids Res 40: 3106–3116.

18. BarkanA, WalkerM, NolascoM, JohnsonD (1994) A nuclear mutation in maize blocks the processing and translation of several chloroplast mRNAs and provides evidence for the differential translation of alternative mRNA forms. EMBO J 13: 3170–3181.

19. Schmitz-LinneweberC, Williams-CarrierR, BarkanA (2005) RNA immunoprecipitation and microarray analysis show a chloroplast pentatricopeptide repeat protein to be associated with the 5′-region of mRNAs whose translation it activates. Plant Cell 17: 2791–2804.

20. LurinC, AndresC, AubourgS, BellaouiM, BittonF, et al. (2004) Genome-wide analysis of Arabidopsis pentatricopeptide repeat proteins reveals their essential role in organelle biogenesis. Plant Cell 16: 2089–2103.

21. ChiSW, HannonGJ, DarnellRB (2012) An alternative mode of microRNA target recognition. Nat Struct Mol Biol 19: 321–327.

22. ValleyCT, PorterDF, QiuC, CampbellZT, HallTM, et al. (2012) Patterns and plasticity in RNA-protein interactions enable recruitment of multiple proteins through a single site. Proc Natl Acad Sci U S A 109: 6054–6059.

23. LaingC, WenD, WangJT, SchlickT (2012) Predicting coaxial helical stacking in RNA junctions. Nucleic Acids Res 40: 487–498.

24. LeontisNB, WesthofE (2003) Analysis of RNA motifs. Curr Opin Struct Biol 13: 300–308.

25. FilipovskaA, RackhamO (2012) Modular recognition of nucleic acids by PUF, TALE and PPR proteins. Mol Biosyst 8: 699–708.

26. LeeS, ChirikjianGS (2004) Interhelical angle and distance preferences in globular proteins. Biophys J 86: 1105–1117.

27. WangX, McLachlanJ, ZamorePD, HallTM (2002) Modular recognition of RNA by a human pumilio-homology domain. Cell 110: 501–512.

28. DamJ, SchuckP (2005) Sedimentation velocity analysis of heterogeneous protein-protein interactions: sedimentation coefficient distributions c(s) and asymptotic boundary profiles from Gilbert-Jenkins theory. Biophys J 89: 651–666.

29. OkudaK, NakamuraT, SugitaM, ShimizuT, ShikanaiT (2006) A pentatricopeptide repeat protein is a site recognition factor in chloroplast RNA editing. J Biol Chem 281: 37661–37667.

30. CrooksGE, HonG, ChandoniaJM, BrennerSE (2004) WebLogo: a sequence logo generator. Genome Res 14: 1188–1190.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2012 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#