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May 25

What is the "major splice donor" and how is it different from the Retroviral Psi packaging element?

According to this article on lentiviral packaging, safe lentiviral pseudoviruses can be produced by excluding gag/pol etc. from the viral genome proper and incorporating them instead with plasmids. These genes will not be packaged into the pseudoviruses because they lack "the HIV-1 elements that must be present in lentiviral vectors" which "include the RNA packaging signal (Ψ), the major splice donor, and the Rev-response element (RRE)." I get what the Ψ packaging signal is, as well as the RRE, but what is the major splice donor? I am surprised we do not have an article for it. Yanping Nora Soong (talk) 09:13, 25 May 2020 (UTC)[reply]

Here I read: "This region [viz. the non-coding part of the HIV genome between the LTR promoter and the first Gag open reading frame] encodes the 5ʹ-untranslated region (5ʹ-UTR) of the HIV RNA genome and contains many post-transcriptional replication signals, including the major splice donor (MSD) that is used in the generation of all spliced HIV transcripts and the packaging signal Ѱ that ensures the selective encapsidation of HIV RNA in assembling virion particles." From Figure 1 in the article I get the impression that MSD and Ψ are adjacent. --Lambiam 20:15, 25 May 2020 (UTC)[reply]

Okay, so this major splice donor will be present in all mRNA transcripts and serve as a packaging signal, whereas a generic 5'UTR or intron would not serve this purpose? Yanping Nora Soong (talk) 22:47, 25 May 2020 (UTC)[reply]

What (I think) I understand from the text in that article, the MSD and the Ψ packaging signal are distinct elements with distinct functions. This seems to be confirmed by the lengthy title of this article: "The packaging signal of simian immunodeficiency virus is upstream of the major splice donor at a distance from the RNA cap site similar to that of human immunodeficiency virus types 1 and 2". --Lambiam 08:15, 26 May 2020 (UTC)[reply]

I understand they are different sites, but I don't actually what the major splice donor does differently compared to the Ψ signal. Would the major splice donor be found in the 5' UTR of all retroviral mRNA transcripts, thus being a reliable packaging signal? Yanping Nora Soong (talk) 11:42, 26 May 2020 (UTC)[reply]

It is not my field, and the scholarly texts I find are research articles, apparently written for an audience of researchers in the field and scanty on explanation. --Lambiam 15:09, 26 May 2020 (UTC)[reply]

But reading e.g. this summary [[1]] I tend to imagine something like this: after the viral RNA has been replicated several times, some of this whole viral genome (let us call it primary RNA) must be spliced to give the different messengers from which the viral proteins (including the capsid's components) are synthesized, and some must remain intact in order to be packaged into the finished capsids. So the MSD seems to control how much of the primary RNA is spliced vs. not spliced. Maybe acting like some kind of promoter for the splicing machinery. 2003:F5:6F08:8200:3179:F503:CF2E:D769 (talk) 18:18, 28 May 2020 (UTC) Marco PB[reply]