Ribosomopathies: Many Questions and A Few
Answers
Nahla A M Hamed*
Professor of Hematology, Alexandria University, Egypt
Submission: May 21, 2018; Published: June 06, 2018
*Corresponding author: Nahla AM Hamed, Professor of Hematology, Faculty of Medicine, Alexandria University, Egypt,
...
Ribosomopathies: Many Questions and A Few
Answers
Nahla A M Hamed*
Professor of Hematology, Alexandria University, Egypt
Submission: May 21, 2018; Published: June 06, 2018
*Corresponding author: Nahla AM Hamed, Professor of Hematology, Faculty of Medicine, Alexandria University, Egypt,
Email:
Abstract
The ribosomopathies are a diverse group of disorders that are caused by mutations in a gene encoding either a ribosomal protein, or a
component of the apparatus required for ribosome biosynthesis. The dysfunction of RPs has been linked to the development and progression of
hematological, metabolic, and cardiovascular diseases and cancer. Ribosome biogenesis appears to be an attractive target for cancer prevention
or therapy
Introduction
Structure and function of ribosomes The ribosomopathies
Ribosomes are essential components of the protein synthesis These are a diverse group of disorders that is caused by
machinery [1]. Ribosomes are large complex molecules [2] mutations in a gene encoding either a ribosomal protein, or a
comprised of ribosomal RNA (rRNA), ribosomal proteins component of the apparatus required for ribosome biosynthesis
(RPs), and small nucleolar RNAs (snoRNAs) [3]. rRNA catalyzes [2]. Clinical features of the ribosomopathies can include bone
peptide bond formation during protein synthesis; RPs optimize marrow failure, developmental abnormalities, and increased
rRNA processing and stabilize the ribosome’s final structure; risk of cancer [3]. Immune defects have also been proposed
and snoRNAs primarily regulate chemical modifications to be a hallmark [2]. However, Ribosome biogenesis disorders
of other RNAs [3]. RNA and protein are assembled into a are highly heterogeneous in their physical manifestations [2].
functional, multi-subunit enzyme [2]. Ribosomes are universally Ribosomal dysfunction can cause a wide range of presentation
responsible for the quality and quantity of proteins in all cells and severities that differ dramatically even among patients with
[4]. RPs has extra-ribosomal functions that are involved in cell the same diagnosis [3]. Despite their heterogeneity at a clinical
proliferation, differentiation, apoptosis, DNA repair, and other level and modes of inheritance, they affect the same biochemical
cellular processes. A subset of RPs also acts as “watch guards” to process [2].
detect the defects in ribosome biogenesis (the synthesis of the
Among the autosomal dominant ribosomopathies are
ribosome) [1].
Diamond–Black fan Anemia (DBA); Treacher Collins syndrome
Ribosomal stress which also has an autosomal recessive form; isolated congenital
The TP53, mTOR, and MYC pathways are evidently each asplenia; and the autosomal dominant form of aplasia cutis
important for ribosome biogenesis. It has become apparent, that congenita. The ribosomopathies inherited in an autosomal
these pathways interact and influence each other [2]. Disruption recessive fashion include Shwachman–Diamond syndrome [2].
of ribosome biogenesis results in ribosomal stress which Some ribosomopathies specifically affect the craniofacial
triggers activation of the p53 signaling pathway, through RPs– skeleton (i.e. Treacher Collins Syndrome), while other
MDM2 interactions, resulting in p53-dependent cell cycle arrest ribosomopathies encompass combinatorial malformations of the
and apoptosis. RPs also regulates cellular functions through craniofacial, axial and/or limb skeletal systems (DBA, Postaxial a
p53-independent mechanisms [1]. Under stress situations, acrofacial dysostosis, Roberts syndrome, Schwachman-Diamond
ribosome activity decreased, protein synthesis is reduced, with syndrome, Cartilage Hair hypoplasia and Bowen-Conradi
subsequent growth arrest [1]. syndrome). Bone marrow failure may or may not be present as
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