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2015 ; 112
(28
): 8608-13
Nephropedia Template TP
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FUS functions in coupling transcription to splicing by mediating an interaction
between RNAP II and U1 snRNP
#MMPMID26124092
Yu Y
; Reed R
Proc Natl Acad Sci U S A
2015[Jul]; 112
(28
): 8608-13
PMID26124092
show ga
Pre-mRNA splicing is coupled to transcription by RNA polymerase II (RNAP II). We
previously showed that U1 small nuclear ribonucleoprotein (snRNP) associates with
RNAP II, and both RNAP II and U1 snRNP are also the most abundant factors
associated with the protein fused-in-sarcoma (FUS), which is mutated to cause the
neurodegenerative disease amyotrophic lateral sclerosis. Here, we show that an
antisense morpholino that base-pairs to the 5' end of U1 snRNA blocks splicing in
the coupled system and completely disrupts the association between U1 snRNP and
both FUS and RNAP II, but has no effect on the association between FUS and RNAP
II. Conversely, we found that U1 snRNP does not interact with RNAP II in FUS
knockdown extracts. Moreover, using these extracts, we found that FUS must be
present during the transcription reaction in order for splicing to occur.
Together, our data lead to a model that FUS functions in coupling transcription
to splicing via mediating an interaction between RNAP II and U1 snRNP.
|Base Sequence
[MESH]
|Humans
[MESH]
|RNA Polymerase II/*metabolism
[MESH]
|RNA Splicing/*physiology
[MESH]
|RNA, Small Nuclear/chemistry/metabolism
[MESH]
|RNA-Binding Protein FUS/metabolism/*physiology
[MESH]
|Ribonucleoprotein, U1 Small Nuclear/*metabolism
[MESH]