|PROSITE documentation PDOC51939 [for PROSITE entry PS51939]|
La and La-related proteins (LaRPs) comprise an ancient superfamily of proteins that are conserved in nearly all eukaryotes, except Plasmodium. These proteins are broadly involved in critical processes of RNA use and metabolism in the nucleus and the cytoplasm. The LaRP superfamily is distinguished by a conserved bipartite RNA-binding unit called the La-module, composed by a Lupus antigen motif (LaM) (see <PDOC50961>) followed by an RNA-Recognition motif (RRM) (see <PDOC00030>). Beyond this, each LaRP family is characterized by distinct family specific domains and motifs that contribute to structure and function. Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU -3'OH. The La-module of these proteins bind the UUU-3'OH, protecting the RNA from degradation, while other domains may be important for RNA folding or others functions. The La and LaRP7 protein families have a C-terminal domain that contains a novel class of atypical RRM, named xRRM (for atypical RRM with extended α3), which uses a unique mode of single- and double-strand RNA binding [1,2,3,4,5].
The overall fold of the xRRM is an RRM, but with several atypical features (see <PDB:<5KNW>). Unusual features of the xRRM include the absence of conserved RNP1 and RNP2 aromatic sequences on the β3 and β1 strands, respectively, typically involved in nucleotide recognition; the presence of an additional helix α3 that lies across the β-sheet surface, where single-stranded nucleotides usually bind; and a C-terminal tail required for RNA binding that is disordered in the free xRRM but forms an α3 extension (α3x) on binding RNA. The front face of the xRRM consists of an antiparallel β-sheet with helix α3 lying across the β-sheet perpendicular to the β-strand axis. The back side of the xRRM consists of α helices. The xRRM interacts with both single- and double-stranded RNA using the β-sheet surface and the C-terminal tail, which forms a helical extension of α3 (α3x) that binds to the RNA major groove [1,2,3,4,5].
The profile we developed covers the entire xRRM domain.Last update:
September 2020 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Jacks A. Babon J. Kelly G. Manolaridis I. Cary P.D. Curry S. Conte M.R.|
|Title||Structure of the C-terminal domain of human La protein reveals a novel RNA recognition motif coupled to a helical nuclear retention element.|
|2||Authors||Singh M. Wang Z. Koo B.-K. Patel A. Cascio D. Collins K. Feigon J.|
|Title||Structural basis for telomerase RNA recognition and RNP assembly by the holoenzyme La family protein p65.|
|Source||Mol. Cell. 47:16-26(2012).|
|3||Authors||Singh M. Choi C.P. Feigon J.|
|Title||xRRM: a new class of RRM found in the telomerase La family protein p65.|
|Source||RNA. Biol. 10:353-359(2013).|
|4||Authors||Eichhorn C.D. Chug R. Feigon J.|
|Title||hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin of 7SK RNA.|
|Source||Nucleic. Acids. Res. 44:9977-9989(2016).|
|5||Authors||Dock-Bregeon A.-C. Lewis K.A. Conte M.R.|
|Title||The La-related proteins: structures and interactions of a versatile superfamily of RNA-binding proteins.|
|Source||RNA. Biol. 0:1-16(2019).|