Structural biology: Ribosomes and Russian dolls

Date:
September 23, 2020
Source:
Ludwig-Maximilians-Universita"t Mu"nchen
Summary:
Maturation of the ribosome is a complex operation. Work now
shows that the 90S precursor of the small 40S subunit undergoes
a 'molting' process, during which it progressively discards its
outermost components.



FULL STORY ========================================================================== Maturation of the ribosome is a complex operation. Work by an Ludwig- Maximilians-Universitaet (LMU) in Munich team now shows that the 90S
precursor of the small 40S subunit undergoes a 'molting' process, during
which it progressively discards its outermost components.


========================================================================== Protein synthesis, programmed by the genetic information encoded
in the DNA, is perhaps the most crucial process that takes place
in biological cells. Proteins are indispensable for all organisms,
because they are responsible for performing a vast range of biological functions. Indeed, the molecular machines that put proteins together --
which are known as ribosomes -- are themselves partly made up of specific proteins. The second vital ingredient of every ribosome is a small set
of specific RNAs, which serve as scaffolds to which ribosomal proteins
can be specifically attached. The synthesis of ribosomes is therefore
an extremely complex, multistep process, which includes both assembly
and maturation stages. This complexity explains why many of the details
of the whole operation are still incompletely understood. Now a group
of researchers led by Professor Roland Beckmann at LMU's Gene Center
has obtained new insights into the maturation phase that gives rise
to the small subunit of the functional ribosome in brewer's yeast. The
study, which was carried out in collaboration with colleagues based in Heidelberg, appears in the leading journal Science.

In the cells of higher organisms, mature ribosomes are composed of two
distinct subunits, each of which contains a long ribosomal RNA (rRNA)
molecule (called 18S in the small and 25S in the large subunit in
yeast). The subunits interact with one another and with the messenger
RNAs that program the synthesis of each protein. In yeast, the smaller
40S subunit is derived from a much larger precursor complex called the
90S pre-ribosome. The 90S precursor particle contains a single (35S)
RNA molecule. The RNAs ultimately associated with each mature subunit are produced by the removal of specific internal and end- fragments. However,
one of the segments the RNA found in the 90S precursor plays an important
role in ensuring that the mature 18S rRNA in the 40S subunit folds into
its correct three-dimensional form.

How the processing of the 35S rRNA is achieved has so far been
unclear. The general idea was that, as the 40S subunit matures, the
processing steps that give rise to the 18S rRNA take place, and the
mature 40S particle eventually 'emerges' from the 90S precursor. The
new study adds new details, which reveal that the process is rather more complicated than that. For a start, a specific enzyme (Dhr1) is required
to ensure that the initial cleavage of the 35S rRNA precursor occurs at
the right position. Dhr1 first exposes the cleavage site, enabling it
to interact with the enzyme Utp24, which cuts the correct fragment off
one end of the 35S rRNA.

In addition, the 'emergence' of the 40S subunit entails an ordered series
of reactions in which the outer shell of the 90S particle is progressively dissociated from the 40S. "It doesn't just go plop," Beckmann remarks. The process is actually reminiscent of the molting of an insect -- shedding
of the integument takes place layer by layer. "It's rather like those
Russian dolls.

When you open one, you find a smaller one nestled inside,"
says Beckmann. - - And with the aid of cryo-electron microscopy,
the specialists in Munich were able to discriminate between the
different three-dimensional complexes characteristic of each step
in the process. Earlier biochemical experiments performed by a team
at the Center for Biochemistry at Heidelberg University (BZH), led by
Professor Ed Hurt, had already cast doubt on the previous en bloc model
by providing evidence for the idea that shedding of the outer layers of
the 90S particle took place stepwise.

The elucidation of such mechanisms is not only of interest from the point
of view of basic research. As Beckmann points out, more and more disorders
have been shown to be related to a lack of intact ribosomes. When errors
occur in the assembly and maturation of these delicate and intricate
molecular machines, they may ultimately lead to a relative dearth of
ribosomes, which then perturbs the delicate equilibrium between protein synthesis and degradation. Among the resulting syndromes are diverse
forms of muscle atrophy, growth anomalies, anemias and certain cancers.


========================================================================== Story Source: Materials provided by
Ludwig-Maximilians-Universita"t_Mu"nchen. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Jingdong Cheng, Benjamin Lau, Giuseppe La Venuta, Michael
Ameismeier,
Otto Berninghausen, Ed Hurt, Roland Beckmann. 90S pre-ribosome
transformation into the primordial 40S subunit. Science, 2020;
369 (6510): 1470 DOI: 10.1126/science.abb4119 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200923124621.htm

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