Enhancer is the cis-acting DNA sequence that can enhance the transcription of an associated gene, when bound by specific transcription factors. The pre-mRNAs are capped, polyadenylated, spliced, edited and transferred from nucleus to cytoplasm. The stability of mRNA is also an important aspect for translation.
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Alternative splicing is a regulatory process during gene expression that enables a single gene coding for multiple proteins. Recent studies indicate that lncRNA can regulate alternative splicing through two main mechanisms. SR splicing factor proteins, such as SRSF1, are a conserved family of proteins involved in RNA splicing regulation in a concentration- and phosphorylation-dependent manner. Different mRNAs have different lifespans, even in a single cell. The steady-state level of a mRNA is determined by the rate of synthesis and degradation.
Modulation of mRNA degradation is an important control point in gene expression to regulate protein synthesis in response to physiological needs and environmental signals. LncRNA can also directly interact with proteins and regulate their stability by retarding protein ubiquitination and degeneration. Androgen receptor AR is a critical risk factor in castration-resistant prostate cancer. Transcription and translation are two main stages in gene expression.
In translation, the ribosomal preinitiation complex, consisting of eukaryotic initiation factors eIFs and ribosomes, is positioned the start codon of the target RNA. The subcellular localization of lncRNAs is associated with their functions.
Telomeric repeat-binding factor-2 TRF2 , a critical component of the shelterin complex, is one of the targets of miRa. LncRNA can act as protein molecular decoy by binding and sequestering proteins, thereby inhibiting their functions [ 54 ]. Glucocorticoid receptor GR plays important role in regulating genes associated with metabolism, development and immune response. Here we will give a brief introduction of the interactions of lncRNA with other molecules.
The Hoogsteen hydrogen binding by a third strand is usually weaker than the Watson-Crick hydrogen bonding. When the proteins introduced by lncRNAs are methylation—related enzymes, these enzymes can induce promotor CpG island methylation or demethylation Figure 1A. When the proteins imported by lncRNAs are histone modifier enzymes Figure 1A , histone modifications can result gene expression, transcriptional silencing, or DNA repair and genomic imprinting.
LncRNA can regulate either neighboring cis or distal trans protein coding genes. The mechanisms of lncRNA regulating gene expression by interacting with other molecule. A lncRNA acting as scaffold binds to chromatin and epigenetic modifier, guide the epigenetic modifier to gene promotor. D lncRNA can act as scaffold for two or more protein, these proteins will act coordinately or act as a complex left. Some antisense lncRNAs can bind to the homologous mRNA at the splice site, thereby masking the splice site and blocking spliceosome assembly [ 69 ].
There is no double that RNA-protein interactions play a crucial role in fundamental cellular processes. LncRNAs can function as protein decoys recruiting or sequester proteins, or act as scaffolds linking different proteins, which may act coordinately or act as a complex Figure 1D left.
Several models have been established to understand how an lncRNA regulates gene expression by protein binding. LncRNAs are able to recruit chromatin modifier to achieve chromatin modification [ 73 ]. LncRNA can bind and stabilize a protein by masking its ubiquitination site, inducing the accumulation of the target protein [ 44 ].
LncRNAs are also able to bind to functional enzymes to inhibit their activities [ 33 ], resulting elevated levels of substrate proteins. Most of lncRNAs are located exclusively in the nucleus, but some of them are located in the cytoplasm or in both nucleus and cytoplasm. Increasing evidence reveals that RNA subcellular location is a very important feature in understanding lncRNA functions.
The nuclear function of lncRNAs are apt to regulate gene expression in cis or in trans. In the nucleus, a lncRNA can accumulate at its transcription site and recruit transcription factors or chromatin modifiers. Genes Dev. Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage.source url
Regulatory RNAs - Basics, Methods and Applications | Bibekanand Mallick | Springer
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