Protein ‘glue’ which holds biomolecules within the nucleolus, identified.


The nucleolus is a crucial membrane-less structure or organelle that takes up about 25% of the nucleus of a mammalian cell.  The largest membrane-less organelle, the nucleolus has been compared to a manufacturing hub, since one of its main functions is to assemble the ribosomes that produce all of the proteins required by cells. The nucleolus is home to a vast array of proteins, RNA and other molecules, however, its molecular foundation is unknown.

Now, a study from researchers at St. Jude Children’s Research Hospital has determined that the protein nucleophosmin (NPM1) serves as glue that holds proteins and RNA together in the nucleolus, showing how NPM1’s structure makes it ideal for the job.  The team state that their findings come amid intense scientific interest in the role liquid-liquid phase separation plays in promoting membrane-less organelle assembly as well as in performing the molecular processes that occur within them.  The opensource study is published in the journal eLife.

Previous studies show NPM1 is an important regulatory protein that is abundant in the nucleolus. NPM1 is known in part for its role in tumour suppression as a binding partner of the tumour suppressor protein ARF.  NPM1 includes segments that fold into a rigid, five-sided pentamer and other segments rich in flexible, negatively charged amino acids that bind transiently to other proteins. Earlier studies from the lab demonstrated how under certain conditions the NPM1 pentamer unfolds into a single disordered strand of amino acids. Data also showed that this disordered strand prevented binding to proteins like ARF that include short amino acid sequences rich in the amino acid arginine.  The current study identifies the interactions that stem from these segments and allow NPM1 to form loose networks with multiple proteins and RNAs within the cell nucleus.

The current study utilised a variety of imaging, structural and biophysical laboratory techniques to identify NPM1 as key to the assembly process within the nucleolus. Results show that the structure of NPM1 allows it to bind to a wide variety of proteins as well as to RNA in different, specific ways that promote phase separation and retain NPM1 and other proteins in the nucleolus. Data findings show that NPM1 forms networks of interactions with other molecules in the nucleolus, loosely gluing nucleolar components together.

Results show that incorporation within the nucleolus required NPM1 binding with both nucleolar proteins that include the arginine-rich segments and ribosomal RNA. The group also identified where on the pentamer protein and RNA binding occurred and how the different bonds promoted condensation into liquid-like droplets.

The team surmise that there are other proteins in the nucleolus that have some of the same features as NPM1, including the negatively charged amino acid tracts.  For the future, the researchers state that this suggests NPM1 is probably not the only protein contributing to phase separation in the nucleolus and needs further investigation.

Source: St. Jude Children’s Research Hospital

 

Cellular environment and organelles by Joel Dubin.

Cellular environment and organelles by Joel Dubin.

 

 

 

One comment

  • Vitthalrao B. Khyade

    “Dr. APIS”
    SCIENCE SPECTRUM
    Objective: To Establish the Repository of Contributions of Eminent Scholars and Information on Science and Culture For The Society.
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    Rudolph Schoenheimer :
    Scientist of the Day (11 September).
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    Rudolph Schoenheimer
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    (Birth: 10 May, 1898 )———————————————( Death: 11 September, 1941 )
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    Rudolph Schoenheimer (May 10, 1898 – September 11, 1941) was a German / U. S. biochemist who developed the technique of isotope tagging of biomolecules, enabling detailed study of metabolism. This work revealed that all the constituents of an organism are in a constant state of chemical renewal.
    Born in Berlin, after graduating in medicine from the Friedrich Wilhelm University there, he learned further organic chemistry at the University of Leipzig and then studied biochemistry at the University of Freiburg[1] where he rose to be Head of Physiological Chemistry.
    He spent the 1930-31 academic year at the University of Chicago.
    In 1933, following the rise of the Nazis to power he emigrated from Germany to the Columbia University to join the department of Biological Chemistry. Working with David Rittenberg, from the radiochemistry laboratory of Harold C. Urey and later together with Konrad Bloch, they used stable isotopes to tag foodstuffs and trace their metabolism within living things.[1]
    He further established that cholesterol is a risk factor in atherosclerosis.[1]
    He suffered from manic depression all of his life,[2] which led to him in 1941 committing suicide using cyanide.[1] He had been honoured with the request to give the Dunham Lecture at Harvard before his death. It was read for him following his death.
    References:
    1. Kennedy, E P (2001), “Hitler’s gift and the era of biosynthesis”, J. Biol. Chem. (published Nov 16, 2001), 276 (46), pp. 42619–31,doi:10.1074/jbc.R100051200, PMID 11559714.
    2. Young, V R; Ajami, A (1999), “The Rudolf Schoenheimer Centenary Lecture. Isotopes in nutrition research”, The Proceedings of the Nutrition Society (published Feb 1999), 58 (1), pp. 15–32, PMID 10343336
    3. Olson, R E (1997), “The dynamic state of body constituents (Schoenheimer, 1939)”, J. Nutr. (published May 1997), 127 (5 Suppl), pp. 1041S–1043S, PMID 9164302
    4. Guggenheim, K Y (1991), “Rudolf Schoenheimer and the concept of the dynamic state of body constituents.”, J. Nutr. (published Nov 1991), 121 (11), pp. 1701–4,PMID 1941176
    5. Ratner, S; Rittenberg, D; Keston, A S; Schoenheimer, R (1987), “The Journal of Biological Chemistry, Volume 134, June 1940: Studies in protein metabolism. XIV. The chemical interaction of dietary glycine and body proteins in rats. By S. Ratner, D. Rittenberg, Albert S. Keston, and Rudolf Schoenheimer”, Nutr. Rev. (published Oct 1987), 45(10), pp. 310–2, PMID 3320825
    6. Shemin, D (1987), “On the impact on biochemical research of the discovery of stable isotopes: the outcome of the serendipic meeting of a refugee with the discoverer of heavy isotopes at Columbia University”, Anal. Biochem. (published Mar 1987), 161 (2), pp. 365–9, doi:10.1016/0003-2697(87)90464-7, PMID 3555154
    7. Sinohara, H (1986), “Rudolf Schoenheimer: a biographical essay”, Seikagaku (published Dec 1986), 58 (12), pp. 1449–70, PMID 3553368
    8. Goldstein, J L (1986), “On the origin and prevention of PAIDS (Paralyzed Academic Investigator’s Disease Syndrome)”, J. Clin. Invest. (published Sep 1986), 78 (3), pp. 848–54, doi:10.1172/JCI112652, PMC 423687, PMID 3528221
    9. Stetten, D (1982), “Rudi”, Perspect. Biol. Med., 25 (3), pp. 354–68, PMID 6763679

    File: Dr.APIS.11.September@Rudolph.Schoenheimer.
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    Acknowledgement: Girija Girish Tambe of Vaishnavi Xerox helped for Collection of images in the Science Spectrum of 11 September, 2016. All the mistakes in the collection of information from website, it’s compilation and communication belongs exclusively to :
    Vitthalrao B. Khyade . Please do excuse for the mistakes.
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    “Dr. APIS”, Shrikrupa Residence, Teachers Society, Malegaon Colony (Baramati) Dist. Pune – 413115. vbkhyade@gmail.com

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    Dr.APIS@World.of.Science.Information
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