Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 290

splicing, editing, 33 and polyadenylation. 34 Heterogeneous ribonucleoproteins bind
to different sets of nascent transcripts (pre-mRNAs) at distinct times during RNA
processing. 35
Therefore, as RBPs are involved in the transcriptional and post-transcriptional
control of RNAs, they regulate gene expression patterns during the body's develop-
ment and remodeling from embryogenesis to adulthood. RNA-binding proteins also
participate in the maintenance of the stem cell state and cell-fate specification.
The signal transduction and activation of RNA (STAR) set of RBPs can be
subdivided into 3 categories: SAM68, SF1, and Quaking-related (QR) subsets.
Members of the STAR set function in pre-mRNA splicing, export, stability, and
translation. Quaking proteins recognizes and binds to a specific sequence in the
3 UTR of target mRNAs. They control muscle development via the Hedgehog
pathway [ 538 ].
Heterogeneous ribonucleoprotein Embryonic lethal, abnormal vision protein-like
molecule ELAV1, or human antigen-R (HuR), selects mRNAs to be exported
to the cytosol for translation, hence contributing to the regulation of myoblast
differentiation [ 539 ]. 36 The RNA-binding protein Hermes (portmanteau for heart,
RNA recognition motif (RRM)-expressed sequence) connects to mature RNAs and
represses cardiogenesis [ 540 ].
The assembly of sarcomeres requires proper amounts of multiple types of
proteins at a given time in a coordinated manner. Contractile proteins assem-
ble into actin-containing thin filaments and myosin-containing thick filaments.
Non-contractile proteins anchor these filaments to Z discs at sarcomere ends.
33 RNA editing is a type of RNA modification that results from the deamination of adenosine to
inosine catalyzed by the ADAR proteins. Target transcripts localize mainly in the nervous system,
where they generate ion channels and G-protein-coupled receptors, such as glutamate and serotonin
receptors [ 536 ].
34 Polyadenylation of mRNAs using polynucleotide adenylate transferase (a.k.a. adenosine triphos-
phate (ATP):ribonucleic acid adenylate transferase, RNA adenylase, polyadenylate synthase,
poly(A) polymerase, and poly(A) hydrolase) that has 2 substrates, ATP and RNA, and 2 products,
diphosphate and RNA with an extra adenosine nucleotide at its 3 end. Polyadenylation of
mRNAs strongly influences their nuclear transport, translation efficiency, and stability. Cleav-
age and polyadenylation-specific factor (CPSF) is a ribonucleoproteic complex (with CPSF1-
CPSF4, CPSF2L-CPSF4L, CPSF6-CPSF7, and nudix, or CPSF25 possible subunits) required in
polyadenylation [ 536 ]. In cooperation with nuclear polyadenylate-binding protein (PABPn1), it
activates polyadenylate polymerase.
35 RNA-binding protein hnRNPa1 is involved in pre-mRNA splicing and nuclear export; hn-
RNPa2b1 in splicing and mRNA transfer; hnRNPc in pre-mRNA packaging, splicing, stability,
and nuclear retention; hnRNPd in mRNA stability; hnRNPf in splicing; hnRNPh in splicing and
polyadenylation; hnRNPk in transcription, pre-mRNA splicing, translation, and regulation, and
mRNA stability; hnRNPl in mRNA export and stability; and hnRNPu in nuclear retention [ 537 ].
36 Cleavage of ELAV1 generates 2 fragments: ELAV1 cleavage products ELAV1CP1 and
ELAV1CP2. The former tethers to transportin-2, thereby allowing non-cleaved ELAV1 to lodge
in the cytoplasm and promoting myogenesis.