User:Kgrudziaz
Please don’t delete any of this. I’m writing a Wikipedia article as an academic assignment and this User Page contains my draft work.
| RNA recognition motif | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| Symbol | RRM | ||||||||
| Pfam | PF00076 | ||||||||
| InterPro | IPR000504 | ||||||||
| PROSITE | PDOC00030 | ||||||||
| |||||||||
RNA recognition motif[edit]
RNA recognition motif (RRM), also known as RNA-binding domain (RBD) or ribonucleoprotein domain (RNP) is a protein domain which main function is single-stranded RNA binding.
Structure[edit]
RRMs are small domains of approximately 90 amino acids. Typical RRM consists of four beta strands and two alpha helices arranged in a β1-α1-β2-β3-α2-β4 fold, where four antiparallel beta stands in the order β4-β1-β3-β2 create a beta sheet and two alpha helices are packed against it. In the central area of beta sheet two highly conserved regions are located. First, called RNP1 is located in β3 strand and constituted of eight amino acids: Lys/Arg-Gly-Phe/Tyr-Gly/Ala-Phe/Tyr-Val/Ile/Leu-X-Phe/Tyr where X can be any amino acid. Second region, called RNP2 is less conserved and was characterised as sequence of six amino acids: Ile/Val/Leu-Phe/Tyr-Ile/Val/Leu-X-Asn-Leu located in the β1 stand. Both sequences play important roles in ligand binding. Loops between alpha-helices and beta-strands as well as N- and C-termianal regions near RRM usually remain disordered but can sometimes create secondary structure elements and often take part in RNA recognition[1].
Multiple RRMs[edit]
In prokaryotic organisms only one RRM domain can be found in one protein. In eukaryotic organisms about 44% of proteins containing RRM is composed of two to six RRMs. Neighbouring RRM domains can be used to recognise long RNA sequences (8-10 nucleotides) and to increase binding affinity and specificity. In some proteins interactions between RRMs can produce loops in their bound RNA or prevent RNA binding[1][2].
RNA recognition[edit]
Known RRM domains recognise single stranded RNA from minimum 2 to maximum 8 nucleotides long. For many RRMs mechanism of ligand binding is similar and involves highly conserved aromatic residues of RNP1 and RNP2. Most commonly two nucleobases from neighbouring nucleotides of RNA interact with aromatic rings located in the position 2 of RNP2 and position 5 of RNP1 and the aromatic ring located in position 3 of RNP1 stacks between two sugar rings of RNA. In other cases different residues of beta-sheet, loops between secondary structure elements and additional N- and C- terminal regions are involved in ligand binding[2]. Although mechanism of ligand binding is well established for many RRMs, universal code that could explain relationship between RRM structure and its ligand sequence remains unknown[3].
Abundance[edit]
Proteins containing RRM are present in organisms of all live kingdoms. RRMs are quite rare in prokaryotes and are one of the most abundant domains in eukaryotes. Up to now (December 2013) more then 1 000 sequences coding RRM domain in prokaryotic organisms are know and more than 30 000 in eukaryotic organisms. In Homo Sapiens genome there are 812 sequences coding RRM[4]. Approximately 0,5-1% of human proteins have at least one RRM domain[2].
Role in cell[edit]
RRM containing proteins take part in all cellular processes involving RNA processing and transport, such as: transcription, splicing (e.g.,SR proteins), alternative splicing (e.g.,RBFOX, SR proteins), 5'-capping and 3'-polyadenylation (e.g.,CSTF2), RNA editing (e.g.,ACF), mRNA export (e.g.,TLS), translation (e.g., eIF4B), RNA degradation[5][6][7][8][9][10]
Protein interaction[edit]
It is known that some RRMs have not only the ability to bind RNA but are also involved in protein-protein interactions. Three classes of interactions between RRMs and proteins can be distinguished:
- between RRM and RRM
Two RRMs usually interact to form an extended surface for RNA binding (e.g., two N-terminal RRMs of hnRNPA1) which would be able to recognise longer RNA sequence, increase binding affinity and specificity. RRM-RRM interaction can also prevent RNA binding or produce additional loops in RNA structure.
- between RRM which binds RNA and another protein
Interaction with another protein can regulate RRMs ability to associate with RNA. Some proteins (e.g., CBP20) can bind its ligand only in contact with another protein.
- between to RRM which does not bind RNA and another protein
There are known some protein containing RRM that are involved in protein-protein interactions and can be part of big protein complexes but do not associate with RNA (e.g., Y14)[2][11][12][13]
qRRM[edit]
Quasi RRMs are protein domains similar to RRMs but have poorly conserved RNP1 and RNP2 sequences. To bind RNA they use loops between the secondary structure elements instead of beat-sheet. qRRMs are present in hnRNP F/H family.They are known to recognise G-track in RNA and take part in regulating alternative splicing[14].
References[edit]
- ^ a b Maris C , Dominguez C, Allain FH (2005). "The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression". FEBS J 272: 2118-2131.
- ^ a b c d Clery A, Blatter M, Allain FH (2008). „RNA recognition motifs: bring? Not quite”. Curr. Opin. Struct. Biol. 18: 290-298.
- ^ Auweter SD, Oberstrass FC, Allain FH (2006). „Sequence-specific binding of single-stranded RNA: is there a code for recognition?” Nucleic Acids Res. 34:4943-4959.
- ^ http://pfam.sanger.ac.uk/family/rrm.
- ^ Long JC, Caceres JF (January 2009). "The SR protein family of splicing factors: master regulators of gene expression". Biochem. J. 417 (1): 15–27.
- ^ Auweter SD, Fasan R, Reymond L, et al. (2006) "Molecular basis of RNA recognition by the human alternative splicing factor Fox-1.". EMBO J. 25 (1): 163–73.
- ^ "Entrez Gene: CSTF2 cleavage stimulation factor, 3' pre-RNA, subunit 2, 64kDa".
- ^ Henderson JO, Blanc V, Davidson NO ( 2001). "Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene". Biochim. Biophys. Acta 1522 (1): 22–30.
- ^ Storlazzi CT, Mertens F, Nascimento A, Isaksson M, Wejde J, Brosjo O, Mandahl N, Panagopoulos I (2003) "Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma." Hum. Mol. Genet.12(18):2349-2358.
- ^ "Entrez Gene: EIF4B eukaryotic translation initiation factor 4B".
- ^ Xu RM, Jokhan L, Cheng X, Mayeda A, Krainer AR (1997) "Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs." Structure 5:559–570.
- ^ Mazza C, Ohno M, Segref A, Mattaj IW, Cusack S (2001) "Crystal structure of the human nuclear cap bind-ing complex." Mol. Cell 8:383–396.
- ^ Lau CK, Diem MD, Dreyfuss G, Van Duyne GD (2003) "Structure of the Y14-Magoh core of the exon junction complex." Curr Biol 13, 933–941.
- ^ Dominguez C, Allain FH (2006). "NMR structure of the three quasi RNA recognition motifs (qRRMs) of human hnRNP F and interaction studies with Bcl-x G-tract RNA: a novel mode of RNA recognition”. Nucleic Acids Res. 34: 3634-3645.