Neuroscience Letters 444 (2008) 11–15
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Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet
The LARK/RBM4a protein is highly expressed in cerebellum as compared
to cerebrum
Thorsten Pfuhl
a
, Alfredo Mamiani
a
, Matthias Dürr
a
, Susanne Welter
a
, Johanna Stieber
a
,
Jasmin Ankara
a
, Michael Liss
b
, Thomas Dobner
c
, Andrea Schmitt
d
, Peter Falkai
d
,
Elisabeth Kremmer
e
, Volker Jung
f
, Stephanie Barth
a
, Friedrich A. Grässer
a,∗
a
Department of Virology, Universitätsklinikum, Haus 47, 66421 Homburg/Saar, Germany
b
Geneart AG, 93059 Regensburg, Germany
c
Institute for Experimental Virology and Immunology, Heinrich-Pette-Institute, 20251 Hamburg, Germany
d
Department of Psychiatry, University of Göttingen, 37075 Göttingen, Germany
e
Institute of Molecular Immunology, Helmholtz Zentrum München – German Research Center for Environmental Health, 81377 München, Germany
f
Department of Urology, Universitätsklinikum, 66421 Homburg/Saar, Germany
article info
Article history:
Received 18 April 2008
Received in revised form 4 July 2008
Accepted 5 August 2008
Keywords:
RBM4
RBM4a
RBM4b
Lark
Hlark
RNA binding motif 4 protein
Monoclonal antibodies
mAb
RISC
Splicing
Alternative spilcing
Tau
Tauopathy
Protein expression
Tumour
Brain
Liver
Kidney
Cerebrum
Cerebellum
abstract
The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human chromosome 11q13.2 and
encode highly similar proteins of 363 and 359 amino acids, respectively. They contain two RNA recognition
motifs (RRMs) and a retroviral-type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and
is also a part of the microRNA-processing RISC complex. In particular, RBM4a is involved in exon 10
inclusion of the tau protein. The function of RBM4b is unknown. With new monoclonal antibodies we
show that RBM4a is detectable in virtually all tissues and cell lines tested while RBM4b was only found in
kidney and liver. Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5 h and 4.5 h,
respectively. To our knowledge, this is the first description of RBM4b protein in human tissue. In human
brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain.
© 2008 Elsevier Ireland Ltd. All rights reserved.
The lark/RBM4 gene is highly conserved from fruit flies to humans
[8] and encodes a protein of the RNA recognition motif (RRM)
class essential for Drosophila melanogaster development and the
circadian rhythm output pathway. In addition to two potential RNA-
recognition motifs (RRMs), the protein contains a CCHC retroviral
∗
Corresponding author. Tel.: +49 6841 162 3983; fax: +49 6841 162 3980.
E-mail address: graesser@uks.eu (F.A. Grässer).
(RT-) type zinc-finger [17]. Lark/RBM4 binds RNA [13,16], inter-
feres with pre-mRNA splicing [11,15] and alters CAP-dependent
translation and IRES-mediated translation following cell stress [12].
In addition, it is part of the microRNA processing RISC complex
[7]. Two highly related copies of the RBM4 gene are present in
close proximity on human chromosome 11q13.2. In the following,
we refer to the hlark/RBM4 genes/proteins as RBM4a and RBM4b.
Because RBM4a also interacts with the Wilms tumour protein WT1
[14] and possibly has a role in the development of neurological
diseases (tauopathies) [9], we generated monoclonal antibodies
0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.neulet.2008.08.017