mRNA Splicing - mRNA post-transcriptional processing/modifications - What is alternative splicing?

[@sandoreszenyi7266]

I don't know how this channel has only 7K subscribers: this is easily some of the most elegantly taught molecular content on all of youtube. This channel will be the reason I passed my molecular biology class.

[@navi09]

I can’t believe I just binged watched all the transcription videos starting from prokaryotic to eukaryotic. I was having a hard time focusing on my studies but your videos are so engaging as well as extremely informative. Loved them all! I really wish your channels blows up. Molecular Biology has never been easier to understand than this. Thank you so much! PS: Next stop - Translation videos! Can’t wait!

[@theCrux]

I am glad the content has been useful :)

[@zackkykada567]

thank you so much for this explanation as i came from an article completely thinking its a hard thing to learn then met your video that gave me light on the process ps:name of the article is "day in a life of a spliceosome"

[@snakepliskin6391]

Honestly it took me like 40 mins to make it through that for all the times i would have to rewind lol! That was amazing though i love the "side notes" you have in there that just inform me of other advanced concepts!

[@leixiao169]

very good job explaining this fascinating process!

[@mathildebour1106]

Clear, precise and great sketches ! Thank you :)

[@deepikaosmania]

great stuff. Please don't stop making videos

[@adrijabanerjee-ek6hw]

Absolute fantastic work

[@jbauman2141]

This is a fantastic, super clear explanation! Thanks, looks like a ton of work

[@dXoverdteqprogress]

Another great video. You should get an award for the board work alone. Quick question. The RNA pol is known to slow down at the intron location to give the splicing mechanism enough time to do its job. Is this sequence specific? On that same note: is the promoter proximal pausing also sequence specific? Thank you.

[@theCrux]

Great questions! 1. Pol II slows down a bit at 3' SS. Pol II elongation rate depends on multiple factors: 1) GC rich regions are difficult to process at high Pol II speed (some introns appear to show bias at the 3' SS) 2) Epigenetic modifications (some methylation marks like H3K79me2 *do fact check me on this*) correlate with faster elongation rate. 3) Some introns can also form G-quadruplex and Pol II tends to slow down there. 4) The relative availability of rNTPs can also affect the pol II elongation rate. 5) Histone enrichment and DNA topology are some other factors that I think can also influence the process (although I doubt there is much literature on this). So, there are some sequence specific features, but I don't think we understand the control the elongation rate of Pol II in great detail, yet. A caveat to all this, is that elongation rate depends on multiple contexts and genes and specific introns. So some introns may have these factors influencing the elongation rate, while other introns will not have these factors. 2. Promoter proximal pausing appears to be primarily regulated via phosphorylation of CTD - the tug-of-war between NELF/DSIF/pTEF-b is usually what determines the balance of release/no-release. I am not aware of studies that look into sequence divergence at proximal non-paused/paused Pol II sites/genes.

[@Anan_233]

prefect sharing，thank you！

[@navinshirodkar3640]

you are amazing, i love your videos !

[@vipikuttu7383]

Amazing 😍 keep going👌

[@MohammedAhmed-pc9ys]

Superb!

[@jorgemanesgarcia4676]

Great video Crux!! I was wondering, could you explain in a bit more detail back-splicing and the functions of circularRNAs? Thanks!

[@theCrux]

Hi Jorge! Back-splicing appears to be an abnormal type of splicing, where 5' end of the pre-mRNA upstream exon is spliced with the 3' end of a downstream exon. Current research isn't sure why/how this occurs mechanistically, but we do know that it forms circular RNAs. Thus, the abnormal splicing forms abnormal circular RNAs (instead of a lariat that typically results in canonical splicing) - they are correlated with pathological conditions. Circular RNAs tend to be more stable because they are circular so exonucleases can't cut them. Their accumulation becomes a problem for the cell. There is some support that SOME circular RNAs serves biological functions like RNA transport, miRNA action etc. but mostly in eukaryotes (especially generated by back splicing) they are considered a problem. Hope this helps 🙂

[@scarletwitchsfan]

200th like 🎉🎉🎉

[@snakepliskin6391]

I have a question on isoform expression... Do cells make mistakes when expressing the isoforms? Like when they try to express one trait will they accidentally express a different gene that is coded for in an isoform? So if a cell starts expressing a gene that codes for multiple proteins and it starts producing more of one of the two proteins on that isoform gene, will it make mistakes and create more of the other protein coded for by the isoform?

[@theCrux]

Typically, the isoform expression is well regulated. And yes, cells can make mistakes in alternative splicing, which typically leads to diseases. You can read about one of the many examples here: 10.1016/j.cell.2016.07.025

[@vardhanpol821]

You need to post more vids bro, for all the helpless students over the world

[@Bckup-jt1xu]

Am I Inside The Microscope?