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1.
Cell Rep ; 34(2): 108578, 2021 01 12.
Article in English | MEDLINE | ID: mdl-33440147

ABSTRACT

Rpb4/7 binds RNA polymerase II (RNA Pol II) transcripts co-transcriptionally and accompanies them throughout their lives. By virtue of its capacity to interact with key regulators (e.g., RNA Pol II, eIF3, and Pat1) temporally and spatially, Rpb4/7 regulates the major stages of the mRNA life cycle. Here we show that Rpb4/7 can undergo more than 100 combinations of post-translational modifications (PTMs). Remarkably, the Rpb4/7 PTM repertoire changes as the mRNA/Rpb4/7 complex progresses from one stage to the next. These temporal PTMs regulate Rpb4 interactions with key regulators of gene expression that control transcriptional and post-transcriptional stages. Moreover, one mutant type specifically affects mRNA synthesis, whereas the other affects mRNA synthesis and decay; both types disrupt the balance between mRNA synthesis and decay ("mRNA buffering") and the cell's capacity to respond to the environment. We propose that temporal Rpb4/7 PTMs mediate the cross-talk among the various stages of the mRNA life cycle.


Subject(s)
RNA Polymerase II/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Animals , Protein Processing, Post-Translational
2.
Neuropsychologia ; 49(10): 2803-16, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21679719

ABSTRACT

Individuals with text-based neglect dyslexia omit words on the neglected side of the sentence or text, usually on the left side. This study tested whether the syntactic structure of the target sentence affects reading in this type of neglect dyslexia. Because Hebrew is read from right to left, it enables testing whether the beginning of the sentence and its syntactic properties determine if the final, leftmost, constituent is omitted or not. The participants were 7 Hebrew-speaking individuals with acquired left text-based neglect dyslexia, without syntactic impairments. Each participant read 310 sentences, in which we compared 5 types of minimal pairs of sentences that differed in the obligatoriness of the final (left) constituent. Complements were compared with adjuncts, obligatory pronouns were compared with optional resumptive pronouns, and the object of a past tense verb was compared with the object of a present tense verb, which can also be taken to be an adjective, which does not require an object. Questions that require a verb were compared with questions that can appear without a verb, and clauses that serve as sentential complements of a verb were compared with coordinated clauses, which are not required by the verb. In addition, we compared the reading of noun sequences to the reading of meaningful sentences, and assessed the neglect point in reading 2 texts. The results clearly indicated that the syntactic knowledge of the readers with neglect dyslexia modulated their sentence reading. They tended to keep on reading as long as the syntactic and lexical-syntactic requirements of the sentence had not been met. In 4 of the conditions twice as many omissions occurred when the final constituent was optional than when it was obligatory. Text reading was also guided by a search for a "happy end" that does not violate syntactic or semantic requirements. Thus, the syntactic structure of the target sentence modulates reading and neglect errors in text-based neglect dyslexia, suggesting that the best stimuli to diagnose mild text-based neglect dyslexia are sentences in which the leftmost constituent is optional, and not required by syntax. Another finding of this study is dissociation between neglect dyslexia at the text and at the word levels. Two of the participants had neglect dyslexia at the text level, manifested in omissions of words on the left side of text, without neglect dyslexia at the word level (namely, without omissions, substitutions, or additions of letters on the left side of words).


Subject(s)
Dyslexia, Acquired/psychology , Pattern Recognition, Visual , Perceptual Disorders/psychology , Reading , Semantics , Adult , Aged , Aged, 80 and over , Female , Functional Laterality , Humans , Male , Middle Aged , Neuropsychological Tests , Surveys and Questionnaires
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