The Scientist - USA (2019-12)

(Antfer) #1

36 THE SCIENTIST | the-scientist.com


as a major component of paraspeckles.
The findings also linked paraspeckles to
the exciting world of lncRNAs at a time
when the notion was just emerging that
lncRNAs are functional, and not simply
transcriptional noise. The debate over
lncRNAs continues today. While there is a
general acceptance that tens of thousands
of lncRNAs are produced by the human
genome, how many of these are functional
is still controversial. NEAT1 has become
an important model lncRNA with a clear
cellular function: forming paraspeckles.
Because NEAT1 is so long—more
than 23,000 nucleotides—it is possible
to label different parts of the RNA and
see them appear in different zones of
individual paraspeckles. A paraspeckle

is roughly spherical, with a shell and
a core, as defined by the distinct pro-
tein and RNA composition of each of
these regions. Using gold labelling and
electron microscopy, Pierron’s group
in Paris, in collaboration with us and
others, showed that the 5' and 3' ends
of NEAT1 are found in the shell, while
the middle sequences of the RNA are
found in the core.^7 (See illustration on
this page.) Another collaborative group
that I was part of, led by Shinichi Nak-
agawa at Hokkaido University, later
confirmed this with super-resolution
imaging.^8 Hirose’s group, working in
concert with Nakagawa’s team, myself,
and many others, found—by providing
seed sequences for various paraspeckle-

Because NEAT1


is so long—more


than 23,000


nucleotides—it is


possible to label


different parts of


the RNA and see


them appear in


different zones


of individual


paraspeckles.


© PEG GERRITY

PARASPECKLE


FORMATION


These tiny subnuclear bodies typically measure 360 nanometers in diameter. They are
composed of a long noncoding RNA (lncRNA) molecule called NEAT1, which serves
as the seed. Proteins that bind to NEAT1 accumulate, self-associate, and recruit other
proteins, forming a mature paraspeckle.

360 nm

PARASPECKLE
PROTEINS (PSPs)

FUS

NEAT1 IncRNA Core Shell

NONO

SFPQ

Other
PSPs

5’ end
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