{PDOC51939}
{PS51939; XRRM}
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* xRRM domain profile *
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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 alpha3),  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 beta3 and beta1 strands,
respectively, typically involved in nucleotide recognition; the presence of an
additional helix alpha3 that lies across the beta-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 alpha3 extension
(alpha3x) on  binding  RNA.  The  front  face  of  the  xRRM  consists  of  an
antiparallel beta-sheet   with   helix  alpha3  lying  across  the  beta-sheet
perpendicular to  the  beta-strand axis. The back side of the xRRM consists of
alpha helices.  The  xRRM  interacts with both single- and double-stranded RNA
using the  beta-sheet  surface  and the C-terminal tail, which forms a helical
extension of alpha3 (alpha3x) that binds to the RNA major groove [1,2,3,4,5].

The profile we developed covers the entire xRRM domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: September 2020 / First entry.

[ 1] Jacks A., Babon J., Kelly G., Manolaridis I., Cary P.D., Curry S.,
     Conte M.R.
     "Structure of the C-terminal domain of human La protein reveals a
     novel RNA recognition motif coupled to a helical nuclear retention
     element."
     Structure 11:833-843(2003).
     PubMed=12842046; DOI=10.1016/s0969-2126(03)00121-7
[ 2] Singh M., Wang Z., Koo B.-K., Patel A., Cascio D., Collins K.,
     Feigon J.
     "Structural basis for telomerase RNA recognition and RNP assembly by
     the holoenzyme La family protein p65."
     Mol. Cell. 47:16-26(2012).
     PubMed=22705372; DOI=10.1016/j.molcel.2012.05.018
[ 3] Singh M., Choi C.P., Feigon J.
     "xRRM: a new class of RRM found in the telomerase La family protein
     p65."
     RNA. Biol. 10:353-359(2013).
     PubMed=23328630; DOI=10.4161/rna.23608
[ 4] Eichhorn C.D., Chug R., Feigon J.
     "hLARP7 C-terminal domain contains an xRRM that binds the 3' hairpin
     of 7SK RNA."
     Nucleic. Acids. Res. 44:9977-9989(2016).
     PubMed=27679474; DOI=10.1093/nar/gkw833
[ 5] Dock-Bregeon A.-C., Lewis K.A., Conte M.R.
     "The La-related proteins: structures and interactions of a versatile
     superfamily of RNA-binding proteins."
     RNA. Biol. 0:1-16(2019).
     PubMed=31752575; DOI=10.1080/15476286.2019.1695712

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