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Illustration of mRNA pseudouridylation by dyskerin and its impact on protein synthesis. Credit: Science Advances (2023). DOI: 10.1126/sciadv.adg1805

How Is Nucleus Involved In Protein Synthesis

RNA has a central role in the cell’s protein production. New research shows that RNA can be altered through various chemical modifications, the function of which is unknown to most. The study was conducted by researchers from the Department of Cellular and Molecular Biology and the Department of Biosciences and Nutrition and was published in the journal Science Advances.

Eukaryotic Protein Synthesis

“Our findings show that already by producing an mRNA (during transcription), the cell can make chemical modifications that can control how that mRNA is translated into protein,” says Chiara Pederiva, postdoc in the Department of Cellular and Molecular Biology. Karolinska Institutet and first author of the study.

“Our findings reveal that an RNA modification called pseudouridylation controls how quickly mRNA is translated into protein. We show which enzyme carries out this modification (dyskerin), when it occurs in the cell (already during transcription), and what happens if this modification does not occur (abnormal protein production).

“Finally, we have found that RNA pseudouridylation is lost in patients with dyskeratosis congenita, a disease associated with increased risk of cancer and premature aging and caused by mutations in the dyskerin enzyme. This opens up the possibility that problems in RNA pseudouridylation contribute to the development of this disease,” says Davide Trevisan, Ph.D. student at the Department of Biosciences and Nutrition, Karolinska Institutet and joint first author of the study.

This provides important information about one of the cell’s most central processes—protein production—and how the cell can control protein production in the cytoplasm from mRNA transcription, which occurs in the cell nucleus. The findings also show a link to a genetic disease.

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The importance of RNA modifications to cellular processes and disease development is an area of ​​research in its infancy. These new findings raise knowledge to a new level and may help develop new therapies.

The study was performed by combining high-throughput sequencing, cell biology and biochemical techniques. “We now want to investigate the scope of this mechanism in detail and use the information to design new treatments against dyskeratosis congenita and cancer,” says Marianne Farnebo, senior author of the study.

More information: Chiara Pederiva et al, Control of protein synthesis through mRNA pseudouridylation by dyskerin, Science Advances (2023). DOI: 10.1126/sciadv.adg1805

Citation: Study shows how mRNA modification controls cellular protein synthesis (2023, August 25) retrieved November 9, 2023 from https:///news/2023-08-modification-mrna-cellular-protein-synthesis.html

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New simulation program offers a way to build microbial cell factories quickly and efficiently 5 minutes ago Poison dart frogs: Personality determines reproductive strategies, research suggests 1 hour ago Turkana stone beads tell a life story of herders in a parched East Africa 5,000 years ago 1 hour ago Webb and Hubble combine to create the most vivid picture of the universe 1 hour ago Researchers develop light-activated protein superglue for fast, precise control accurately of cells and tissues 1 hour ago Deep sea pressure found to store food for microbes in the abyss 1 hour ago Lightning identified as main cause of boreal forest fires, threatens carbon storage 1 hour ago Zooplankton in the ocean and freshwater are rapidly escalating global environmental threat of plastics, study finds 1 hour ago Liquid metals shake up centuries-old chemical engineering processes 1 hour ago Study finds rate of Greenland glacier retreat has doubled over two decades last 1 hour ago This amazing work of art (Figure 5.7.1) shows a process that occurs in the cells of all living things: the production of proteins without fasting. This process is called protein synthesis and it actually consists of two processes –

, where the translation takes place. During translation, the genetic code in mRNA is read and used to make a polypeptide. These two processes are summarized by the central dogma of molecular biology: DNA → RNA → Protein.

Transcription is the first part of the central dogma of molecular biology: DNA → RNA. It is the transfer of genetic instructions in DNA to mRNA. During transcription, a strand of mRNA is made to complement a strand of DNA. You can see how this happens in Figure 5.7.2.

Protein Synthesis (diagram) Diagram

Figure 5.7.2 Transcription uses the sequence of bases on one strand of DNA to create a complementary strand of mRNA. Triplets are groups of three consecutive nucleotide bases in DNA. Codons are complementary sets of bases in mRNA.

Transcription begins when the enzyme RNA polymerase binds to a region of a gene called the promoter sequence. This signals the DNA to be released so that the enzyme can “read” the DNA bases. The two strands of DNA are named based on whether they will be used as a template for RNA or not. The strand that is used as a template is called the template strand, or it can also be called the ntisense strand. The sequence of bases on the opposite strand of DNA is called the non-coding or sense strand. After the DNA is opened and RNA polymerase attached, RNA polymerase moves along the DNA, adding RNA nucleotides to the growing mRNA strand. The DNA template strand is used to create mRNA through complementary base pairing. Once the mRNA strand is complete, it is cleaved from the DNA. The result is an mRNA strand that is almost identical to the coding strand DNA – the only difference is that DNA uses the base thymine and mRNA uses uracil instead of thymine

Not yet ready for translation. At this stage, it is called pre-mRNA and must undergo further processing before leaving the nucleus as mature mRNA. Processing may include splicing, editing, and polyadenylation. These processes modify the mRNA in different ways. Such modifications allow a single gene to be used to produce more than one protein.

Translation is the second part of the central dogma of molecular biology: RNA → Protein. It is the process in which the genetic code enters

Translation Stock Illustration

After transcription in the nucleus, the mRNA exits through a nuclear pore and enters the cytoplasm. In the region of the mRNA containing the methylated cap and start codon, the small and large subunits of the ribosome bind to the mRNA. These are then joined by a tRNA containing the anticodons that match the start codon in the mRNA. This group of molecules (mRNA, ribosome, tRNA) is called the initiation complex.

TRNA continues to bring amino acids to the growing polypeptide according to complementary base pairing between codons in mRNA and anticodons in tRNA. As a tRNA moves to the ribosome, its amino acid is transferred to the growing polypeptide. Once this transfer is complete, the tRNA leaves the ribosome, the ribosome moves one codon length down the mRNA, and a new tRNA enters with its corresponding amino acid. This process is repeated and the polypeptide grows.

At the end of the mRNA coding is a stop codon which will end the elongation phase. The stop code does not require a tRNA, but rather a type of protein called a release factor, which will cause the entire complex (mRNA, ribosome, tRNA, and polypeptide) to fall apart, releasing all the components.

Once a polypeptide chain is synthesized, it can undergo additional processes. For example, it can take on a folded shape due to interactions between its amino acids. It can also bind to other polypeptides or different types of molecules, such as

Protein Synthesis (1.2.3)

How proteins are made by Nicolle Rager, National Science Foundation at Wikimedia Commons has been released into the public domain (https://en.wikipedia.org/wiki/Public_domain).

Transcription from the National Human Genome Research Institute, (reworked and vectorized by Sulai) on Wikimedia Commons has been released into the public domain (https://en.wikipedia.org/wiki/Public_domain).

Parker, N., Schneegurt, M., Thi Tu, A-H., Lister, P., Forster, B.M. (2016, November 1). Microbiology [online]. Figure 11.15 Translation in bacteria begins with the formation of the initiation complex. IN

The process by which DNA is copied (transcribed) into mRNA in order to transfer the information needed for protein synthesis.

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Deoxyribonucleic acid – the molecule that carries the genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses.

A large family of RNA molecules that carry genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression.

A large RNA and protein complex that acts as the site of RNA translation, building proteins from amino acids using messenger RNA as a template.

The gelatinous material that makes up most of a cell within the cell membrane and, in eukaryotic cells, surrounds the nucleus. The organelles of eukaryotic cells, such as mitochondria, endoplasmic reticulum, and (in green plants) chloroplasts, are found in the cytoplasm.

Study Shows How Modification Of Mrna Controls Cellular Protein Synthesis

A nucleic acid of which many different types are now known, including messenger RNA, transfer RNA, and ribosomal RNA.

A class of biological molecule composed of linked amino acid monomers that are the most versatile macromolecules in living systems and serve crucial functions

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