Q.After VDJ gene rearrangement at the IgH locus is completed there seem to remain (dependent on splicing) several copies of (different) J segments at the end of the now complete VDJ heavy chain. - ie it is more like a VDJJJJ chain where the number of Js depends on the D->J rearrangement. - For example in the picture the rearranged sequence is shown to be V(H1) D(H26) J(H5) J(H6) C(H1).So my question is what happens after the VDJ rearrangement. - Does transcription of the VDJJC (using above example) proceed as one piece and is then maybe spliced to VDJ(H5)C before expression or does the final protein actually contain two J segments? A.The 3' J segments remain in the DNA and are transcribed through then spliced out of the RNA during processing, leaving only the one J sequence in the final mRNA. This is because although there is a donor (3') splice site downstream of every J the next upstream acceptor (5') splice site is at the beginning of the CH1 exon; so according to the rules of mRNA splicing the first donor site (which is at the end of the rearranged J) will be joined to the next acceptor site and thus CH1 splicing out all intervening RNA.Q.A second question which follows logically from this is what happens when there are several V segments at the beginning: eg. If V -> DJ rearrangement occurs so that the result is V(H1) V(H2) D(H26) ...Is a transcript of VVD... made and V(H1) is spliced out or how is this regulated? A.The major transcript comes from the rearranged V region. This is because the V region promoter is pretty weak and requires proximity to the enhancer (located within the intron between the final J and the first constant exon) to be effective. There are low level transcripts detectable from unrearranged V's but these probably don't read through to the rearranged VDJ or do so at such low frequency as to be negligible. |
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