11.13:
lncRNA – Long Non-coding RNAs
Long non-coding RNAs or lncRNAs can regulate gene expression and other cellular processes. They are widespread and are found in plants, animals, bacteria, and viruses; however, they show low sequence conservation between different species.
LncRNAs are RNA transcripts longer than 200 nucleotides that are not translated into proteins; however, most are processed the same way as precursor mRNA through splicing and the addition of a 5’ cap and 3’ poly-A tail.
Compared to protein synthesis, RNA synthesis takes less energy and occurs more rapidly. As RNA is produced in the nucleus, it can be immediately used for gene regulation and can provide a faster response than proteins, which need to be imported from the cytoplasm.
LncRNA can perform their functions through several different mechanisms. When present near DNA, lncRNA can act as a scaffold for proteins by forming multiple stem-loop structures where proteins can bind and carry out their function, like chromatin-modifying proteins or transcriptional activators and repressors.
Like microRNA, lncRNA can act as guide RNA where its one part binds to various protein complexes whereas another part can selectively base pair with target DNA region and thereby helps in localization of the protein complexes.
LncRNA can act as alternative binding sites or sponges, sequestering some molecules away from their target location. For example, lncRNAs bind to microRNAs and prevent their interaction with their target mRNA.
LncRNA can base-pair with a complementary region in mRNA. This base-pairing can inhibit pre-mRNA splicing by hiding particular splice sites or can block the translation of mature mRNA.
Some lncRNA also carry exons and produce small peptides of unknown function.
LncRNAs are emerging as a significant player in additional cellular processes such as chromatin modifications and epigenetic regulation, as well as several diseases such as cancer and neurological diseases
11.13:
lncRNA – Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA) which are more than 200 nucleotides in length. LncRNAs play a vital role in chromatin modification, regulation of gene expression, cell differentiation, and the immune response. Though named non-coding RNA, some lncRNAs can produce short peptides. LncRNAs are present in many tissues but particularly abundant in the brain and other parts of the central nervous system.
LncRNA can be classified based on their genomic location. Some lncRNAs are synthesized from regions between two genes and are known as large intergenic non-coding RNAs (lincRNAs). LncRNAs are also produced from the regions within genes and include sense lncRNA synthesized from the sense DNA strand and antisense lncRNA produced from the anti-sense DNA strand. Intronic lncRNAs are another class of lncRNAs that are produced from the introns present in a gene.
LncRNAs can also be classified by their function. Guide lncRNA directs specific protein complexes to their target genes to perform different functions such as chromatin modification and transcriptional regulation. A well-studied example of guide lncRNA is Hox transcript antisense intergenic RNA (HOTAIR) which guides the Polycomb Repressive Complex 2, a transcriptional repressor complex, to the HOXD locus. Some lncRNAs act as a scaffold for specific protein binding, as seen in the telomerase RNA component (TERC) which acts as a scaffold for binding of the telomerase complex. LncRNA can also act as a molecular sponge or decoy and sequester regulatory molecules like proteins and microRNA from their target genes. For example, the lncRNA PANDA sequesters nuclear transcription factor Y subunit alpha away from its target genes to prevent p53-mediated apoptosis.
lncRNAs play an important role in cancer development and can act as tumor suppressors or promoters. The abnormal expression of several lncRNAs has been observed in a tumor-specific manner. For example, MALAT1 and XIST lncRNAs are associated with brain cancer whereas HOTTIP and HOTAIR lncRNAs are associated with lung cancer. These cancer-associated lncRNAs can be used as a diagnostic biomarker as well as novel therapeutic targets for cancer treatment.
Suggested Reading
- Kung, Johnny TY, David Colognori, and Jeannie T. Lee. "Long noncoding RNAs: past, present, and future." Genetics 193, no. 3 (2013): 651-669.
- Rinn, John L., and Howard Y. Chang. "Genome regulation by long noncoding RNAs." Annual Review of Biochemistry 81 (2012): 145-166.
- Balas, Maggie M., and Aaron M. Johnson. "Exploring the mechanisms behind long noncoding RNAs and cancer." Non-coding RNA Research 3, no. 3 (2018): 108-117.
- Ma, Lina, Vladimir B. Bajic, and Zhang Zhang. "On the classification of long non-coding RNAs." RNA Biology 10, no. 6 (2013): 924-933.
- Marchese, Francesco P., Ivan Raimondi, and Maite Huarte. "The multidimensional mechanisms of long noncoding RNA function." Genome Biology 18, no. 1 (2017): 206.