Light Chain DNA Undergoes VJ Rearrangements

Expression of both k and X light chains requires rearrangement of the variable-region V and J gene segments. In humans, any of the functional VX genes can combine with any of the four functional JX-CX combinations. In the mouse, things are slightly more complicated. DNA rearrangement can join the VX1 gene segment with either the JX1 or the JX3 gene segment, or the VX2 gene segment can be joined with the JX2 gene segment. In human or mouse k light-chain DNA, any one of the Vk gene segments can be joined with any one of the functional JX gene segments.

Rearranged k and X genes contain the following regions in order from the 5' to 3' end: a short leader (L) exon, a non-coding sequence (intron), a joined VJ gene segment, a second intron, and the constant region. Upstream from each leader gene segment is a promoter sequence. The rearranged light-chain sequence is transcribed by RNA polymerase from the L exon through the C segment to the stop signal, generating a light-chain primary RNA transcript (Figure 5-4). The in-trons in the primary transcript are removed by RNA-processing enzymes, and the resulting light-chain messenger

Germ-line K-chain DNA

L VK1

LVk23 LVKn

Rearranged K-chain DNA

Primary RNA transcript mRNA

Nascent polypeptide

K light chain

Vk Jk

Polyadenylation _ RNA splicing L V J Ck

Poly-A tail

Translation

FIGURE 5-4

Kappa light-chain gene rearrangement and RNA processing events required to generate a k light-chain protein. In this example, rearrangement joins Vk23 and Jk4.

RNA then exits from the nucleus. The light-chain mRNA binds to ribosomes and is translated into the light-chain protein. The leader sequence at the amino terminus pulls the growing polypeptide chain into the lumen of the rough en-doplasmic reticulum and is then cleaved, so it is not present in the finished light-chain protein product.

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