Ribosomes and Diseases

The ribosome is a complicated molecular machine that produces proteins from amino acids during a process known as protein synthesis or translation. Protein synthesis is a basic function that all living organisms should indeed undertake.

Ribosomes are distinct cell organelles found in both bacterial and mammalian cells.  In every living cell, ribosomes are essential for protein synthesis.

They deliver tRNAs containing amino acids to the ribosome’s acceptor site. It attaches to tRNA and begins the process of adding amino acids to the growing protein chain.

Ribosomes Structure

A ribosome is a ribonucleoprotein, meaning it contains both RNA and protein. It is divided into two parts, one of which is smaller and the other larger.

The two subunits are connected through interactions between rRNAs in one subunit and proteins in the other.

In both plant and animal cells, ribosomes are situated inside the cytoplasm.

The following components make up the ribosome structure:

• It can be found in 2 different parts of the cytoplasm.
• The cytoplasm is strewn with them.
• Eukaryotes contain 80S ribosomes, and prokaryotes have 70S.
• RNA makes up about 62 percent of ribosomes, while proteins make up the balance.
• Free and bound ribosomes have alike and structure that is linked to protein synthesis.

Ribosome Function: The following are some of the main ribosome functions:

• One of the most significant ribosome functions is to assemble amino acids into proteins that are required for biological processes.
• The generation of mRNA from DNA is the consequence of the DNA transcription process.
• The nucleus generates mRNA, which is then transported to the cytoplasm to initiate protein synthesis.

Ribosome Location: They are found in the cytosol, some linked to the membrane of the coarse endoplasmic reticulum and others free-floating.
They are used to convert DNA (deoxyribonucleic acid) to proteins, and no rRNA is permanently linked to the RER; instead, they release or bind according to the type of protein they are combining. Up to 10 million ribosomes can be found in a single animal or human cell, and many ribosomes can be linked to the same mRNA strand, forming a POLYSOME.

Ribosome Biogenesis

Ribosomes are the cellular factories that manufacture proteins. The process of generating ribosomes, known as ribosome biogenesis, is a complicated and energy-intensive process involving hundreds of variables. Multiple enzymes, transcription regulators, chaperones, nuclear export proteins, and other factors all work together to ensure that ribosomal RNA (rRNA) is folded correctly and integrated with ribosomal proteins (r-proteins). Saccharomyces cerevisiae, a single-celled model organism, has made significant progress in identifying the mechanisms involved in ribosome formation.

Furthermore, because the RNA and protein moieties of ribosomes, as well as the ribosome biogenesis mechanism, are highly conserved from yeast to humans, what we discovered in yeast applies to humans in general. Ribosome biogenesis is so critical for cell growth that a growing yeast cell needs to manufacture about 2000 ribosomes each minute, accounting for 60% of total cellular transcription. 

Ribosome Disease and Disorder

Ribosomopathy

The aetiology of a diverse range of disorders known as ribosomopathies is caused by defects in ribosome synthesis and function. Ribosomopathies are disorders caused by mutations in RPs or factors involved in Pol I transcription and rRNA processing, resulting in ribosome manufacturing or assembly being disrupted. Several ribosomopathies have characteristics such as inherited bone marrow failure, which is marked by a decrease in the number of blood cells as well as a proclivity for cancer. Skeletal deformities and growth retardation are examples of other symptoms.

Treacle – Treacher Collins syndrome 

Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial ailment that affects the ears, eyes, and facial bones, especially the lower jaw and cheek.

Treacle is a nucleolar phosphoprotein that is thought to be involved in rDNA transcription and 18S rRNA methylation.

Shwachman–Diamond syndrome

Bi-allelic mutations in the SBDS protein cause Shwachman–Diamond syndrome (SDS), which disrupts its capacity to connect GTP hydrolysis by the GTPase EFL1 to the release of eIF6 from the 60S subunit. SDS affects various systems in the body, causing bone deformities, pancreatic malfunction, and neurocognitive dysfunction. In human cells, SBDS associates with the 60S subunit, and in yeast models, it plays a function in subunit joining and translational activation.

5q- myelodysplastic syndrome

The acquired haploinsufficiency of RPS14, a component of the eukaryotic small ribosomal subunit, is linked to 5q-myelodysplastic syndrome (MDS) (the 40S). Depletion of RPS14 in human CD34(+) cells is sufficient to mimic the 5q- deficiency of erythropoiesis while sparing megakaryocytes, indicating that RPS14 is required for 40S assembly.

Cirhin – North American Indian childhood cirrhosis 

Cirrhosis of childhood in North American Indians is an autosomal recessive condition found in the Ojibway-Cree people of northwestern Quebec. The condition begins with newborn jaundice and progresses to cirrhosis of the bile duct. Only liver transplantation, which is necessary by early adolescence, is a viable option.

Alopecia, Neurological defects, and Endocrinopathy syndrome (ANE syndrome) 

Alopecia, neuropathy, and endocrinopathy syndrome (ANE syndrome) is a clinically heterogeneous autosomal recessive condition. Patients with ANE syndrome have a variety of symptoms, including hair loss, mental retardation, progressive loss of motor ability beginning in their second decade of life, hypogonadism, central adrenal insufficiency, short stature, microcephaly, and a variety of other skeletal and skin abnormalities.

Shwachman-Bodian-Diamond syndrome (SDS) 

Shwachman-Bodian-Diamond syndrome (SDS), like ANE syndrome, is an autosomal recessive pleiotropic illness. Pancreatic insufficiency is likely caused by the replacement of pancreatic tissue with adipose tissue, hematologic defects such as neutropenia and, in rare cases, anaemia and/or thrombocytopenia, skeletal abnormalities, short stature, enlarged liver with elevated liver enzymes, endocrine abnormalities, defects in T- and B-cell function, and a proclivity for leukaemia are all symptoms.

Conclusion

Ribosomes are required for cell survival and proliferation. Due to the critical importance of these complexes, it was formerly thought that mutations in ribosomes or ribosome biogenesis factors would be fatal. However, a variety of ribosome biogenesis illnesses have been found in recent decades. The elucidation of the molecular mechanisms underlying them remains a difficulty in the research.