The RPL10 gene and its corresponding protein are fundamental components within human cells. They play a broad role in maintaining cellular health and function, contributing to the intricate processes that underpin life at the cellular level.
Understanding RPL10
RPL10 stands for Ribosomal Protein L10, highlighting its association with ribosomes. The RPL10 gene contains the instructions for building the RPL10 protein. This gene is located on the X chromosome. The RPL10 protein, composed of 214 amino acids, is predominantly found in the cytoplasm and within the nucleus. It is also a component of the cell’s protein-making machinery, the ribosome.
RPL10’s Fundamental Role in Protein Production
RPL10’s primary function is its integral role in ribosomes, particularly within the large 60S ribosomal subunit. Ribosomes are complex cellular machines responsible for translating genetic information from messenger RNA (mRNA) into proteins, a process called protein synthesis. RPL10 contributes to the assembly and stability of these ribosomal structures, ensuring they can perform their protein-building tasks. It is incorporated into the 60S subunit during a late stage of maturation in the cytoplasm.
Within the ribosome, RPL10 is positioned on the inter-subunit side of the large subunit, near the central protuberance. This placement allows it to organize the architecture of the aminoacyl-tRNA binding site, a pocket where transfer RNA (tRNA) molecules carrying amino acids arrive during protein synthesis. RPL10 is also involved in the rotation of ribosomal subunits during the elongation phase of translation, the step where the protein chain is extended. This involvement includes facilitating aminoacyl tRNA movement and contributing to translation control.
Beyond Ribosomes: RPL10’s Diverse Cellular Functions
Beyond its direct involvement in ribosome assembly and protein synthesis, RPL10 also performs “extra-ribosomal” roles, functions independent of the ribosome. The observation that RPL10 is expressed at higher levels in rapidly dividing embryonic tissues compared to adult differentiated tissues suggested its involvement in development and differentiation. Studies indicate RPL10’s participation in cell growth and cell division processes.
RPL10 has been implicated in programmed cell death, also known as apoptosis, by participating in signaling cascades. It has been shown to interact with various cellular factors, including the transcription regulator c-Jun and the proto-oncogene c-Yes, both of which are involved in cell proliferation, migration, and differentiation. These diverse roles highlight how a single protein can have multiple, sometimes interconnected, functions within the complex cellular environment.
RPL10 and Human Disease
Dysfunction, mutation, or altered expression of RPL10 have been linked to various human health conditions. Mutations in the RPL10 gene are associated with specific types of cancer, particularly T-cell acute lymphoblastic leukemia (T-ALL). The recurrent R98S missense mutation in RPL10 is found in approximately 8% of pediatric T-ALL cases. This mutation impairs cellular proliferation and leads to an accumulation of reactive oxygen species, causing mitochondrial dysfunction and reduced ATP levels.
RPL10 R98S mutant leukemia cells can overcome high oxidative stress by increasing IRES-mediated translation of the anti-apoptotic factor B-cell lymphoma 2 (BCL-2), resulting in BCL-2 protein overexpression. This mutation also affects the JAK-STAT signaling pathway, which controls cellular proliferation and survival, by overexpressing its proteins and enhancing its activation. Beyond cancer, mutations in RPL10 have also been linked to neurodevelopmental disorders, including X-linked intellectual disability, microcephaly, seizures, and growth retardation. A missense mutation, p.K78E, has been shown to disrupt neurodevelopment and cause X-linked microcephaly by affecting translational efficiency and increasing apoptosis in brain cells.