PathwayType: signaling

Organ: generic

Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101

Organ_System: generic

Tissue: generic

NodeType: Pathway

Description: Eukaryotic translation is the process by which messenger RNA (mRNA) is translated into polypeptides. Pathway is built manually using published studies.

Notes: Headnote: RNA gene silencing is the process of downregulation or entire suppression of gene expression in a sequence-specific manner at the mRNA level by noncoding RNA molecules. Signaling description: In all organisms, the mechanism for RNA silencing involves cutting of double-stranded RNA (dsRNA) into smaller pieces. When dsRNA is exogenous, such as viral RNA, it is imported directly into the cytoplasm and cleaved into short fragments. The initiating dsRNA may also be endogenous, originating in the cell, and expressed from RNA-coding genes in the genome. The cutting of dsRNA into smaller pieces is carried out by DICER1 in an ATP-dependent reaction. DICER1 cleaves dsRNA into two classes of smaller RNAs including microRNAs (miRNAs) and small interfering RNAs (siRNAs) that are 21-25 nucleotides long. The miRNAs are expressed polycistronically and endogenously. Let-7 (miR-let-7) family genes code for miRNAs that are highly conserved across species in sequence and function. The miRNA genes are generally transcribed by RNA polymerase II. The dsRNA structure of the hairpins in primary-miRNA (pri-miRNA) is recognized by DGCR8 which cleaves the RNA and releases the hairpins to form precursor-miRNA (pre-miRNA). Pre-miRNA hairpins are exported from the nucleus in a process involving exportin 5 (XPO5). Silencing RNA (siRNA) is a short dsRNA that results from being processed by DICER1 which cleaves exogenous long dsRNAs. The siRNAs have 2 strands with a 5' phosphate group and a 3' hydroxyl group. Outcome effects: As a result, two dsRNA pathways converge at the RISC complex. Each siRNA and miRNA is unwound into two single-stranded RNAs (ssRNAs), the passenger strand and guide strand. The passenger strand is degraded and the guide strand is incorporated into the RISC complex. A recent consensus model suggests that EIF2C2 is the core component of the RISC complex that directly receives the double-stranded siRNA and cleaves the siRNA passenger strand. In siRNA-guided RNA silencing, RISC complex cleaves the target mRNA at a single site in the center of the duplex region between the guide siRNA and the target mRNA, resulting in gene silencing. In contrast, miRNAs typically have incomplete base pairing to a target and thus may inhibit translation of many different mRNAs with similar sequences. Cellular proteins interacting with DICER1, such as FMR, TARBP2, and PRKRA, are also key regulators of RISC complex and DICER1 activity.

Source: Cell Process

CellType: generic

Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-fc2e420b-bcd2-49ea-88a6-e6c1c144e700

urn:agi-pathway:uuid-fc2e420b-bcd2-49ea-88a6-e6c1c144e700