Regulation of human Mcl-1 by a divergently-expressed antisense transcript

Related Experiment Video

Updated: Dec 12, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

7.8K

S M Ali Hosseini Rad1, Grace Min Yi Tan1, Aarati Poudel1

  • 1Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.

Gene
|August 11, 2020
PubMed

Insights

Researchers discovered a new RNA mechanism controlling Mcl-1 (myeloid cell leukemia 1) expression. This long non-coding RNA, mcl1-AS1, downregulates Mcl-1, impacting cell viability and offering potential cancer therapy targets.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • RNA Biology

Background:

  • Mcl-1 (myeloid cell leukemia 1) is a key anti-apoptotic protein in the Bcl-2 family, crucial for lymphocyte function and implicated in oncogenesis.
  • Mcl-1 has a short half-life, primarily regulated by miRNA and proteasomal degradation.
  • Existing regulatory mechanisms do not fully explain Mcl-1 expression control.

Purpose of the Study:

  • To identify novel regulatory mechanisms controlling Mcl-1 expression at the RNA level.
  • To characterize the function and mechanism of a newly identified long non-coding RNA (lncRNA) affecting Mcl-1.
  • To explore the therapeutic potential of targeting this regulatory pathway in cancer.

Main Methods:

  • Reporter assays to confirm promoter location.
  • Tetracycline-inducible system to control mcl1-AS1 expression.
  • shRNA to inhibit mcl1-AS1.
  • Bioinformatics analysis for RNA-RNA interactions.
  • Cell viability assays (HEK293 cells).

Main Results:

  • A novel lncRNA, mcl1-AS1, was identified that negatively regulates Mcl-1 expression at both mRNA and protein levels.
  • The promoter for mcl1-AS1 is located within the Mcl-1 coding region, indicating a divergent transcription mechanism.
  • Inducible expression of mcl1-AS1 decreased HEK293 cell viability, while its inhibition reversed drug sensitivity.
  • Bioinformatics predicted direct binding of mcl1-AS1 to Mcl-1 transcripts, suggesting transcriptional regulation.

Conclusions:

  • A novel bi-directional promoter and lncRNA (mcl1-AS1) regulatory axis controlling Mcl-1 expression has been identified.
  • This finding provides new insights into Mcl-1 regulation beyond miRNA and proteasomal pathways.
  • Targeting the mcl1-AS1/Mcl-1 interaction may offer therapeutic strategies for cancer and enhance anti-cancer T lymphocyte function.
Keywords:
Antisense transcriptLOC107985203Long non-coding RNAMcl-1

More Related Videos

Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells07:19

Identifying Targets of Human microRNAs with the LightSwitch Luciferase Assay System using 3'UTR-reporter Constructs and a microRNA Mimic in Adherent Cells

Published on: September 28, 2011

36.6K
CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis10:40

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis

Published on: April 25, 2022

2.7K

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.6K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.2K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.3K