RTCB ligase is an enzyme found in cells. It plays a role in maintaining the integrity and function of cellular components.
What is RTCB Ligase?
RTCB ligase, also known as RNA 2′,3′-cyclic phosphate terminal phosphodiesterase and RNA ligase, is an enzyme. Enzymes are proteins that accelerate specific chemical reactions within cells. RTCB ligase acts as a molecular “sealer,” connecting broken RNA strands.
This enzyme processes and repairs RNA molecules, which carry genetic information and perform various cellular functions. It is unique in its ability to join RNA ends with specific chemical structures. RTCB ligase is the only 3′-5′ RNA ligase identified in human cells.
The Mechanism of RNA Repair
RTCB ligase repairs specific types of RNA damage, particularly those with 2′,3′-cyclic phosphate and 5′-hydroxyl termini. This enzyme functions through a two-step pathway, beginning with the hydrolysis of the 2′,3′-cyclic phosphodiester end to a 3′-monophosphate. This prepares the RNA for ligation.
Following hydrolysis, RTCB ligase catalyzes the formation of a new phosphodiester bond, joining the 3′-monophosphate end to a 5′-hydroxyl end. Guanosine triphosphate (GTP) supplies the energy for this activity, reacting with RTCB ligase in the presence of manganese to form a covalent RTCB-guanylate adduct.
This process allows RTCB ligase to efficiently reseal breaks in RNA strands. Unlike some other RNA ligases that require a separate “healing” step to modify RNA ends before ligation, RTCB ligase directly processes these specific termini.
RTCB Ligase in Cellular Processes
Beyond its general role in RNA repair, RTCB ligase participates in several specialized cellular pathways. One function is its involvement in transfer RNA (tRNA) splicing. Pre-tRNA molecules, precursors to functional tRNAs, contain introns that must be removed.
RTCB ligase is a component of the tRNA ligase complex in metazoans, which joins the cleaved tRNA halves after intron removal. This process is necessary for tRNA maturation, as tRNAs help translate genetic code into proteins. Without proper tRNA splicing, protein synthesis would be impaired.
The enzyme also plays a role in the unfolded protein response (UPR), a cellular stress response. When misfolded proteins accumulate in the endoplasmic reticulum, the UPR activates to restore cellular balance. RTCB ligase is responsible for splicing the XBP1 mRNA, a key step in activating a UPR branch that manages protein folding stress.
Implications for Health and Disease
Dysfunction or mutations affecting RTCB ligase can have consequences for human health. Impaired function is linked to specific neurological conditions, including pontocerebellar hypoplasia type 10 (PCH10).
PCH10 is a rare, genetic neurodevelopmental disorder characterized by severe psychomotor developmental delay, progressive microcephaly, and spasticity. Brain abnormalities, including mild atrophy of the cerebellum, pons, and corpus callosum, are often observed. The disease often presents with intellectual disability and epilepsy.
Research continues to explore RTCB ligase as a potential therapeutic target. Understanding the precise mechanisms by which its dysfunction leads to diseases like PCH10 could inform the development of interventions.