Question

If antisense methods reduced the production of Progerin by altering splicing, but no immediate effect was on nuclear blebbing, how would you explain this? ( Hint- when would you be able to replace Progerin in the nuclear lamina?)

Answer 1

Well, there are some terms that we better define first: The nuclear lamina is an structure formed by proteins that give form to the nucleus and plays some other crucial roles in the nuclear processes, like DNA repairing, e.g. There is one lamina protein that sometimes has a point mutation that triggers a different route during mRNA splicing and lead to a non functional lamina that has recieved the name Progerin, because it produces progeria. One symptom Progerin presence is an abnormaal nuclear form called nuclear blebbing. Antisense methods are capable of interfering with splicing and correct the errors made that produce Progerin. The thing is, the antisense therapy succesfully corrected the splicing and Progerin is not being produced any more, but then the nucleus just keeps showing the blebbing. The question is just: why?

Well, the nucleus is already formed, it already has lamina pieces giving structure, and Progerin is already there. Antisense methods for modigying splicing won't take the stablished Progerin away. There is only one stage in cell cycle that is actually the oportunity to replace nuclear lamina: cell division. Mitosis is the nuclear division, and it requires the nuclear memebrane, along with the lamina, to get destroyed and form new ones for the daughter cells. The nuclear membrane replacement occurs during Telophase.

That is why we cannot see an immediate effect of antinsense treatment over the nuclear structure.