ROLE OF mRNA IN EMBRYONIC DEVELOPMENT
147
a regulator of transcription, either directly (in which case, it would never
have been converted into protein and would be degraded without leaving
the nucleus; Harris, 1963), or after translation into protein. There are
some recent indications in favor of such an interpretation (Attardi et al.,
1966; Houssais and Attardi, 1966; Scherrer et al, 1966; Warner et al.,
1966; Soeiro et al, 1966).
If the second model proposed in the Introduction accounts for
most experimental data, this does not mean that the other models are
entirely excluded. The presence of stable mRNA in differentiated cells
suggests the existence of some type of regulation at the translation level.
This regulation would complement the primary selection of the information that is likely to occur at the DNA level. The secondary regulation
could have something to do with the translation rate of mRNA. It is
hard to conceive that a differentiated cell would translate at maximum
speed all the mRNA that it has accumulated in stable form. It seems
more likely that each cell, once differentiated, stores some mRNA in an
inactive form, which, however, allows a ready utilization if the cell
happens to divide and to double its protein content. The selection of the
information to be transcribed, in other words, the type of mRNA synthesized during embryonic development would thus occur at the chromosomal level. The lifetime and the translation rate of mRNA might very
well be controlled at the ribosomal level.
So far as the selection of the information is concerned, it is by no
means impossible that it involves a modification of DNA itself (Scarano
and Augusti-Tocco, 1967). Methylation of DNA might inhibit the
transcription of some genes or groups of genes in differentiated cells. It
remains, however, to be proved that this DNA modification is a cause
and not a consequence of differentiation itself. Methylation takes place
after the synthesis of DNA (Gold et al., 1963; Srinivasan, and Borek,
1964) and must, therefore, be re-established after each replication in one
of the daughter DNA strands. This implies the intervention of methylation enzymes at each cell division. Such periodical adjustments would not
be necessary to ensure a permanent inactivation of some DNA sites if
DNA underwent transmissible
alterations arising from the conversion of
bases (Scarano and Augusti-Tocco, 1967). These modifications would
occur in early development and differ from one cell line to another. They
could affect definite DNA sites, which would play the role of transcription initiators. The proposed modifications would result in blocking the
transcription of all the genes controlled by the altered initiator. A whole
group of genes could thus be definitively switched off in certain cell lines.
147
a regulator of transcription, either directly (in which case, it would never
have been converted into protein and would be degraded without leaving
the nucleus; Harris, 1963), or after translation into protein. There are
some recent indications in favor of such an interpretation (Attardi et al.,
1966; Houssais and Attardi, 1966; Scherrer et al, 1966; Warner et al.,
1966; Soeiro et al, 1966).
If the second model proposed in the Introduction accounts for
most experimental data, this does not mean that the other models are
entirely excluded. The presence of stable mRNA in differentiated cells
suggests the existence of some type of regulation at the translation level.
This regulation would complement the primary selection of the information that is likely to occur at the DNA level. The secondary regulation
could have something to do with the translation rate of mRNA. It is
hard to conceive that a differentiated cell would translate at maximum
speed all the mRNA that it has accumulated in stable form. It seems
more likely that each cell, once differentiated, stores some mRNA in an
inactive form, which, however, allows a ready utilization if the cell
happens to divide and to double its protein content. The selection of the
information to be transcribed, in other words, the type of mRNA synthesized during embryonic development would thus occur at the chromosomal level. The lifetime and the translation rate of mRNA might very
well be controlled at the ribosomal level.
So far as the selection of the information is concerned, it is by no
means impossible that it involves a modification of DNA itself (Scarano
and Augusti-Tocco, 1967). Methylation of DNA might inhibit the
transcription of some genes or groups of genes in differentiated cells. It
remains, however, to be proved that this DNA modification is a cause
and not a consequence of differentiation itself. Methylation takes place
after the synthesis of DNA (Gold et al., 1963; Srinivasan, and Borek,
1964) and must, therefore, be re-established after each replication in one
of the daughter DNA strands. This implies the intervention of methylation enzymes at each cell division. Such periodical adjustments would not
be necessary to ensure a permanent inactivation of some DNA sites if
DNA underwent transmissible
alterations arising from the conversion of
bases (Scarano and Augusti-Tocco, 1967). These modifications would
occur in early development and differ from one cell line to another. They
could affect definite DNA sites, which would play the role of transcription initiators. The proposed modifications would result in blocking the
transcription of all the genes controlled by the altered initiator. A whole
group of genes could thus be definitively switched off in certain cell lines.