Created by Tracy Kim Kovach.
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- How is the binding of miRNAs, mentioned at1:02, regulated? Or do they always bind complementary mRNA strands? If that is the case, can you give me an example of a gene that would always be silenced? Thanks :-)!(7 votes)
- I'm not sure if I fully understand your question, but I will attempt to give you an answer.
An important part of a miRNA is what is called the "seed region". MiRNAs on average are about 21 nucleotides long, but there doesn't need to be perfect complementary binding between the entire miRNA and the mRNA it is targeting. Only the seed region (about 3-8 nucleotides) needs to perfectly match between the miRNA and the mRNA for regulation to occur.
The degree to which binding is complementary or not also seems to affect whether the mRNA is simply inhibited or if it is completely degraded. For example if the miRNA and mRNA perfectly bind the mRNA would be degraded, if the match was say, 50% complementary, it seems the mRNA is left intact but is just prevented from being translated.
It isn't as simple as miRNA 1 inhibits mRNA of gene 2. One miRNA can target many genes and each gene has multiple miRNAs that target it. For example, collagen (important structural protein in the body) is regulated by at least 20+ miRNAs (if not more). However, miR29 specifically inhibits collagen mRNA expression (as an example). Some miRNAs can also have a positive influence on gene expression so, overall it is very hard to get a "big picture" idea of what will be the net regulation of a gene if you only know the abundance of one miRNA that regulates it.
Also, sometimes the miRNA are actually coded as introns within the gene it is regulating. So when the gene is expressed, it will have miRNAs there ready to regulate its expression.
Hope that helps.(8 votes)
- what is the difference between hnRNA and PremRNA?(2 votes)
- Precursor mRNA is a type of hnRNA (heterogeneous nuclear RNA), but hnRNA can specifically refer to nuclear RNA transcripts that never end up going to the cytoplasm as mRNA (that is, the unprocessed primary transcripts).(4 votes)
- How do miRNAs actually work, though? Do they simply pair up with complementary base pairs on the mRNA and they (I guess) cut the mRNA molecule preventing transcription? What about the degradation instead? I am little confused on the actual mechanism....(3 votes)
- miRNA is actually one of the few types of RNAs classified as RNA interference (RNAi). These groups of RNAs are closely associated with the Argonaute (AGO) family proteins. AGO binds with one RNA strand, creating an RNAi-induced silencing complex (RISC), to facilitate the interactions with the complementary target mRNA. Specifically for miRNA, they are not fully complementary to the mRNA, so a part of it is bound while the rest is not. This is because the main function of the miRNA is to stop translation of the mRNA by hindering it from being processed by the ribosome, hence silencing the gene expression. If it were to be fully complementary (like small interfering RNAs, or siRNAs), it could cause an activation of a region in the AGO protein that cleaves and degrades the mRNA.(2 votes)
- "snRNA + snRNP = spliceosome" is confusing because snRNP already contains snRNA. It should say "5 snRNA + >150 proteins = spliceosome".(2 votes)
- You mention transesterification is how the spliceosome connects the two parts of the pre-mRNA together. But looking at the structure of RNA, I don't see any ester groups?(2 votes)
- Sorry for the late response, but this interested me as well so I had to find out.
In splicing pre-mRNA, two transesterification processes are performed by the spliceosome for the excision of introns and the ligation of exons.
The first of the 2 processes involves an intermediate lariat structure, in which a 2'5' phosphodiester bond between the 5' guanosine residue of the intron and a certain adenosine residue near the 3' end of the intron is formed. In other words, a phosphodiester transfer occurs to exchange a 3'-5' bond for a 2'-5' bond in the formation of a lariat structure.
The second transesterification reaction is in order to ligate exons. Similar to the first one, 3'-5' phosphodiester bonds are exchanged in order to connect the coding parts of the pre-MRNA together, rather than cleaving them and creating a lariat structure for the decomposition of the introns.
Sorry if this was a little wordy, I felt that the information was contextual. Nonetheless, to summarise, the phosphodiester bond transferral between parts of mRNA constitute the transesterification processes that are involved in its splicing.(1 vote)
- Do ncRNA's undergo any post-transcriptional modifications or are they mature and fully functional immediately after they are released from RNAP? I am struggling to find out about ncRNA transcription and whether they undergo methylation/ polyadenylation or any other modifications :)(2 votes)
- so the miRNA basically prevents a mRNA from expressing. So what does a cell do if it needs the gene product, that is if it wants to overcome miRNA inhibition of the particular gene?(2 votes)
- So telomerase is an snRNA?(1 vote)
- Telomerase is a ribonucleoprotein, it is a complex between an RNA and a protein.(2 votes)
Voiceover: What is a non-coding RNA? A non-coding RNA, or an ncRNA, as it is abbreviated, is a functional RNA molecule that actually skips this last step and is not translated into a protein. In other words, they just go directly from transcription into an RNA molecule and then go off to perform any number of vital functions within the cell. There are many examples of non-coding RNAs, including micro RNAs, ribosomal RNAs, transfer RNA, the list goes on and on. As we go through each of these different types and examples of non-coding RNAs, you'll start to see that there's sort of an emerging theme, here. That is that most of these non-coding RNAs participate in either transcription or translation in one capacity or another. Let's start off with micro RNAs. Micro RNAs, or miRNAs, function in transcriptional and post transcriptional regulation of gene expression. They do this by base paring with complementary sequences within mRNA, or messenger RNA, molecules. This usually results in gene silencing through translational repression or target degradation. In essence, the mRNA to which these micro RNAs bind are prevented from being translated or they are sent on a pathway for degradation. The next set of non-coding RNAs that we'll be talking about are all involved in translation. The first of which is ribosomal RNA. Ribosomes are the cellular machinery used to translate mRNA into proteins. It is made up of one type of RNA molecule, ribosomal RNA. Transfer RNAs are an adapter molecule that links the codons in an mRNA strand to the corresponding amino acids. This is another type of non-coding RNA that you'll see in translation. The thrid type is called snow RNA, which stands for small nucleolar RNA. It's a class of small RNA molecules that guide covalent modifcations of ribosomal RNA, transfer RNA, and small nuclear RNAs, primarily through methylation, which is the addition of methyl groups, or pseudouridylation, which is the addition of an isomer of the nucleoside uridine. Another class of non-coding RNAs are the small nuclear RNAs, or snRNAs, not to be confused with the snow RNAs, the small nucleolar RNAs that we just talked about. Small nuclear RNAs get their name from the fact that the average length of these RNA molecules is approximately 150 nucleotides. Their primary function is in the processing of pre-mRNA in the nucleus. They also aid in the regulation of transcription factors or a particular RNA polymerase, RNA polymerase two, as well as maintaining telomeres, which are the regions of repetitive nucleotide sequences at the end of a chromotid, which protects the end of the chromosome from deterioration during chromosomal replication. SnRNA can be associated with a set of specific proteins and form complexes that are called small nuclear ribonucleic proteins, or snRNPs or sometimes people just call them snRPs. There is a special snRP complex called the spliceosome, made up of five small nuclear RNAs and over 150 proteins that is responsible for splicing, or removing, the introns contained in messenger RNA, which is a major step in the post transcriptional modification that takes place in the nucleus of eukaryotes. The way the the spiceosome does this is that it binds to specific sequences in the pre-messenger RNA strand and performs two sequential transesterification reactions that splice out the intron and then [lagate] the two exons to form a mature mRNA. Now you know a little bit more some examples of non-coding RNAs and some of the functions that they perform within the cell.