1.1 Non-coding RNAs The central dogma of molecular biology states that genetic information is conveyed from DNA to mRNA to protein implying that proteins are the main functional genetic output (Crick 1970). Even those few early known non-protein-coding RNAs (ncRNAs) such as transfer RNA, ribosomal RNA, snoRNAs and splicosomal RNAs were in the end required for mRNA processing and translation. The dogma might still be applicable to prokaryotes whose genome consists of approx. 90 % protein-coding genes. In eukaryotes, however, only about 2 % of the genes are protein-coding (Alexander et al. 2010) and those have been studied intensively. The remaining major fraction of the genomic output has for a long time been …show more content…
1.2 Long non-coding RNAs Although the heterogeneous group of long non-coding RNAs (lncRNAs) account with approx. 80 % for the majority of ncRNAs in the mammalian transcriptome (Kapranov 2007), miRNAs have been in the main focus of ncRNA research in the last years. However, there is recent increase in publications describing key functions of lncRNAs in central biological processes (Taft et al. 2010) and diseases.
Trying to categorize non-coding transcripts, lncRNAs have been defined as > 200 nt long sequences with low or no protein-coding potential. They are weakly conserved between species and undergo (in most cases) 5- capping, canonical polyadenylation and splicing just like mRNAs. LncRNAs can also be grouped by their genomic proximity to neighboring coding transcripts (Johnsson et al. 2014):
- Sense
- Antisense, when overlapping with exons of another transcript on the same or opposite strand
- Intronic, when derived from an intron of another transcript
- Bidirectional, when its expression and a neighboring coding transcript on the opposite strand is initiated in close genomic proximity
- Intergenetic, when transcripted from a sequence between
Genes expression is what encodes many proteins to give function to a cell. It involves many steps that mostly include transcription and translation. Transcription alone does not play a role in gene expression (Erster Lect. 24). There are many post-transcriptional regulatory mechanisms that have been found to be involved. These mechanisms are a part of RNA processing. One of this can occur through alternative splicing. This is when exons of the same gene are spliced together to produce different mRNA molecules (Reece, et al. 372). Regulating gene expression also occurs during translation. mRNA lifespan within the cytoplasm is significant when it comes to determining the arrangement of protein synthesis. These mRNA molecules tend to be degraded by enzymes moments
Finally it was found that a total of 62.1 % to about a 74.7% of the human genome was covered by either proceed or by the help of primary transcript.
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Recent advantages in genome-wide analyses have revealed that roughly 90% of the human genome is transcribed, yet less than 3% of the genome consists of protein-coding genes (Wu et al., 2013). The remaining genes are transcribed as noncoding RNAs (ncRNAs), which resemble mRNA in length and splicing structures yet do not encode any proteins (Wu et al., 2013). It has been debated whether all of the ncRNA transcripts are functional due to their low expression levels and low evolutionary conservation. However, many functional ncRNA have
MicroRNAs (miRNA) are small noncoding RNA, usually 17-25 nucleotides long that are able to bind complementary sequences of target messenger RNA (mRNA) and to induce both their degradation and translational repression (Fortunato, et al 2014). They are one of the most significant classes of non-coding RNA molecules (eg. small interfering RNA (siRNA) and ribozymes) that act within the cell. MiRNAs are also evolutionary conserved in different species from plants to humans and are encoded by their respective genes (Bader, 2012).
siRNA are a form of molecular RNA, they are formed from a long double stranded piece of RNA. The dsRNA is cleaved into siRNA segments by the endonuclease DICER, these segments range from 21-25 nucleotides in length. The siRNA becomes part of the RISC complex, one strand is removed, and the remaining strand binds to its exact compliment in the mRNA. At this point exonucleases will enter and degraded the cleaved mRNA.
Most genes in plants and animals contain regions that code for polypeptides, called exons, with noncoding sequences called introns in between. Both introns and exons are transcribed from DNA to RNA, then RNA splicing occurs to remove the introns. Introns can contain nucleotide sequences that regulate gene activity. The splicing process may contribute to controlling the flow of mRNA from nucleus to cytoplasm. Sometimes splicing occurs in different ways, to produce different mRNA molecules from the same transcript.
This study identifies conserved cis sequences as the primary determinant of RNA editing evolution, but does not rule out a role for either trans factors or Adar proteins. It also opens up future research into how cis sequence changes alter RNA editing level.
This study shows that 6% of the entire annotated non-coding and coding gene transcripts are overlapping with small RNAs. Highly specific subcellular positioning is found for both unannotated & annotated short RNA.
The RNA-induced-silencing complex is used for gene regulation and in defense against viral and bacterial infections. The RISC is loaded with small dsRNAs that will guide the complex through base-pairing interactions to specific messenger RNA targets, which the RISC will help degrade. Once degraded, no more protein can be made from these mRNAs. The RNA-induced silencing complex can silence targeted genes through several mechanisms. It can work to repress translation during protein synthesis, interfere with the transcript level through mRNA degradation, or work at the level of the genome itself and eliminate DNA/form degrading materials. Heterochromatin is a degrading material that can be created to modify or suppress genes in the RISC (MacRae
microRNAs (miRNAs) are a short ( about 22-26 nt length ) non coding RNA that involved in regulating gene expression at the level of post-transcription or translation and apparently control a broad range of processes of multicellular organisms including cellular differentiation, proliferation and apoptosis via targeting mRNA and cause their degradation or protein translation inhibition. miRNA transcribed from long pri-miRNA in the nucleus then processed by Dicer enzyme in the cytoplasm to form mature miRNA that incorporate in RNA induced silencing complex (RISC) to enhance their functions.
Transcription in eukaryotes is one of the most vital processes of life that involves a highly controlled and regulated systematic series of events that is mediated through various key factors. The process of transcription occurs when the genetic information stored within DNA becomes activated through the synthesis of complementary mRNA and is thus regulated by RNA polymerases. There are three types of RNA polymerases that distinctively transcribe a specified set of genes. RNA polymerase I and III transcribe genes that have terminal products such as ribosomal subunits, tRNA and small nuclear RNA. For example, RNA polymerase I is located in the nucleolus of eukaryotic cells and is responsible for transcribing 18S, 5.8S,
In the nucleus of our cells, there contains DNA which is what contains the genetic information that our body uses. However to use that genetic information, a protein needs to be made. This all starts in a nucleus in our cells where we begin with transcription. There a helicase splits apart a DNA sequence into two strands, one strand containing codons, and the other containing anti-codons. These codons consist of any triplet of the four nitrogen bases: adenine, thymine, cytosine, and guanine. The complementary base-pair rule states that adenine only connects to thymine and cytosine only connects to guanine. A copy is made of the original template that becomes RNA. Once transcription is finished, mRNA exits the nucleus through the indoplasmic
In eukaryotic cells, pre-mRNA undergoes extensive post-transcriptional modifications to become mature mRNA. The modifications to pre-mRNA include 5’ end capping, 3’ end cleavage and polyadenylation, and the splicing of introns (Gu and Lima, 2005). The spliceosome is a large
One of the fundamental discoveries of the 20th century was that DNA was the genetic code’s physical structure (Watson & Crick, 1953) and, since then, many studies have disclosed the complicated pattern of regulation and expression of genes, which involve RNA synthesis and its subsequent translation into proteins.