Chemistry Reference
In-Depth Information
8.3.2
A Journey from the Transcription Site to the Nuclear Envelope
The mechanism of RNA movement in the nucleus has been addressed by various
approaches [32
35]. One of the hypotheses was that the mRNPs moved from
transcription sites to the nuclear envelope guided by some internal structures similar
to a railroad, and driven by receptors or a transporting complex. Since the elements
of the cytoskeleton, such as actin, nuclear myosin and other related proteins are
found in the nucleus and have even been shown to be involved in the transcriptional
process [36
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38], it has been proposed that nuclear transport machinery that relied on
these skeletal structures, including nuclear motor proteins, might exist. Although
FRAPexperiments onGFP-actin protein show that actin polymerization occurs in the
nucleus and that those structures are highly dynamic [39], their involvement in
nuclear transport has never been observed to date. Insteadmany studies inferred that
the movement of mRNPs is a combination of Brownian motion and ATP-dependent
movements [19, 35]. Most of the questions focused on the relevance and the actual
meaning of the ATP requirement in RNA movements inside the nuclear environ-
ment. Since directed movements are never observed in the nucleus, the energetic
demand may not supply molecular motors but more likely could be used to release
RNPs from stalling during random interactions with nuclear structures on their way,
such as dense chromatin domains, chromatin scaffolds or the cytoskeleton. Rather
than imagine RNP moving on tracks [40], we can envisage the particles moving by
diffusion inside a system of interconnected sinusoidal channels of
fluid phase
bounded by dense chromatin domains [41]. The RNPs will travel in this network of
interchromatin space and occasionally interact with other complexes and/or domains
becoming trapped within areas of high-density chromatin. Reversion fromstationary
tomobile depends on the consumption of ATP [19, 35]. Single particle tracking shows
that RNP motion is energy-independent and not directed [23]. The observation of
corralled, and in rare cases, constrainedmovements highlights the existence of dense
and inaccessible structures hindering the free diffusion of largemolecular complexes
such as mRNPs (Figure 8.2). ATP has an essential role in chromatin remodeling;
decondensation of chromatin after energy depletion could be responsible for
affecting motility by trapping mRNPs within high-viscosity regions of DNA strands.
The caveat in the ATP-depletion experiments is that drug treatments have many
pleiotropic effects that impair a clear discrimination between direct or indirect
causes.
The RNP could dynamically interact with the environment and change its protein
partners during the journey from transcription site to the nuclear envelope,
eventually arriving at the proper composition to interact with the export machin-
ery [42
-
44]. The correct processing of the mRNA will deposit speci
c proteins on
the transcript, like
flags indicating that the particle is ready to be exported, or
whether it still needs processing or has to be retained and degraded. Some proteins
involved in mRNA transport are (respectively yeast/mammalian homolog) Yra1p/
Aly of the REF (RNA and Export Factor binding) family of hnRNP-like proteins and
Mex64p/TAP [43
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45]. The
first pair is an RNA-binding protein and the second the
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