John’s corrections

Author: klmr

conclusion.tex

@@ -66,10 +66,10 @@ \subsection{Regulation of \abbr{trna} gene expression}
 Although \trna[s] have a “canonical” role — to act as adapters in the process of
 translation — this of course does not preclude other roles. In fact, there is
 evidence that ties \trna-derived fragments to different regulatory roles. As
-mentioned in the introduction, about ten per cent of the bases in the \trna[s]
-transcript are post-transcriptionally modified. Some of these modifications
-impact the stability of the transcript. For example, it is known that
-cytosine-\num{5} methylation in the anticodon loop of \trna[s], which is
+mentioned in the introduction, about ten per cent of the bases in a typical
+\trna[’s] transcript are post-transcriptionally modified. Some of these
+modifications impact the stability of the transcript. For example, it is known
+that cytosine-\num{5} methylation in the anticodon loop of \trna[s], which is
 prevalent in actively transcribed \trna[s], inhibits endonucleolytic cleavage.
 Absence of this methylation leads to cleavage and the accumulation of \threep
 and \fivep fragments \citep{Thompson:2008}. Furthermore, there is evidence that
@@ -78,32 +78,33 @@ \subsection{Regulation of \abbr{trna} gene expression}
 
 But not only the \fivep fragment of \trna[s] is catalytically active: the
 \threep ends of specific \trna[s] have been shown to act as primers for the
-transcription of endogenous retroviruses such as \hivi \citep{Litvak:1994} in a
-highly sequence-specific manner. In general, the expression of such retroviruses
-is detrimental for the cell and, by implication, excess abundance of specific
-\trna-derived fragments affects the cell’s fitness negatively. This exerts a
-selective pressure to evolve a mechanism for suppressing such fragments. One way
-of depleting their abundance is to downregulate the expression of originator\todo{ugly, better word?}
-\trna genes in response to the detection of excess \trna fragments.
+transcription of endogenous retroviruses such as \hivi in a highly
+sequence-specific manner \citep{Litvak:1994}. In general, the expression of such
+retroviruses is detrimental for the cell and, by implication, excess abundance
+of specific \trna-derived fragments affects the cell’s fitness negatively. This
+exerts a selective pressure to evolve a mechanism for suppressing the expression
+of such fragments. One way of depleting their abundance is to downregulate the
+expression of the \trna genes from which they are derived in response to the
+detection of excess \trna fragments.
 
 In sum, the regulatory role of \trna transcripts adds another dimension to the
 need for the regulation of their abundance. In fact, the dependence on specific
 enzymes (such as \protein{mmu}{NSUN2} in mouse) to methylate \trna[s], and thus
 to ensure their stability hints at the fundamental importance of preventing the
 formation of excess \trna-derived fragments \citep{Blanco:2014}.
 
-The precise mechanism of the \trna gene expression regulation remains unclear.
-Corroborating previous reports \citep{Oler:2010}, I have found some evidence
-that \trna gene activity correlates with specific histone marks. However, it is
-unclear whether this is a cause or a consequence of differential regulation, and
-it is insufficient to account for differences in the expression of \trna genes
-in close vicinity. Furthermore, there is so far no mechanism for the dynamic
-feedback necessary for effecting the compensatory effect between genes in an
-isoacceptor family.
+The precise mechanisms that regulate the expression of \trna genes remain
+unclear. Corroborating previous reports \citep{Oler:2010}, I have found some
+evidence that \trna gene activity correlates with specific histone marks.
+However, it is unclear whether this is a cause or a consequence of differential
+regulation, and it is insufficient to account for differences in the expression
+of \trna genes in close vicinity. Furthermore, there is so far no mechanism for
+the dynamic feedback necessary for effecting the compensatory effect between
+genes in an isoacceptor family.
 
 \subsection{Absence of evidence for codon bias-dependent translation efficiency in mammals}
 
-Despite the existence of larger variations in codon usage between subsets of
+Despite the existence of large variations in codon usage between subsets of
 genes, some of which are cell type specific, I was unable to find evidence for a
 regulatory effect of this codon bias on translation rates via higher adaptation
 to a cell type specific \trna anticodon isoacceptor pool in mammals. On the
@@ -114,10 +115,10 @@ \subsection{Absence of evidence for codon bias-dependent translation efficiency
 if present at all, plays a negligible role in mammalian systems. It will be
 interesting to see how this controversy will unfold.
 
-If true, this implies that codon bias has not conserved the regulatory role it
-plays in unicellular organisms of all domains of life \colorbox{yellow}{REF},
-where it is well established that codon bias influences translation efficiency
-to control gene-specific expression levels. Why would this central role of codon
+If true, this implies that, in mammals, codon bias has not conserved the
+regulatory role it plays in unicellular organisms \colorbox{yellow}{REF}, where
+it is well established that codon bias influences translation efficiency to
+control gene-specific expression levels. Why would this central role of codon
 bias be present in unicellular organisms but not in complex multicellular
 animals? The following is an attempt at an explanation.
 
@@ -149,10 +150,10 @@ \subsection{Absence of evidence for codon bias-dependent translation efficiency
 
 I suggest that these two factors — the relatively higher complexity of
 transcriptional regulation in mammals, and the higher impact of variation in
-\trna gene transcription on variation in
-\trna availability and thus on translation efficiency in unicellular organisms —
-is sufficient to explain the results we observe here as well as established
-results reported in the literature.
+\trna gene transcription on variation in \trna availability and thus on
+translation efficiency in unicellular organisms — are sufficient to explain the
+results we observe here as well as established results reported in the
+literature.
 
 At the end of the project outlined in \cref{sec:codons}, I have started
 exploring other potential sources of the cell type-specific codon bias observed
@@ -168,7 +169,7 @@ \subsection{The extended \abbr{pol3} transcriptome}
 The \pol3 \chipseq data generated for the projects presented in this thesis
 provides a wealth of information beyond just \trna gene activity.
 \Cref{sec:pol3} takes a brief glimpse at genome-wide \pol3 binding and confirms
-that \pol3 binding can be used to assess gene activity of genes with known
+that \pol3 binding can be used to assess the activity of genes with known
 \pol3-driven transcription.
 
 In particular, I was able to assess binding of \pol3 to the promoter region of
@@ -206,7 +207,7 @@ \subsection{Codon usage adaptation}
 subsets of the transcriptome remains wide open. \gc bias, in particular, is
 worth exploring further. On the one hand, I observed a robust correlation
 between \gc bias and codon usage, and we know that codon usage can sometimes be
-predicted from intergenic \gc bias \citep{Chen:2004}. On the other hand,
+predicted from intergenic \gc content \citep{Chen:2004}. On the other hand,
 \citet{Duret:2002} show that, at least in \species{dmel} and \species{cel}, \gc
 bias is uncorrelated with codon usage bias.